![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 11 to 35 of 61. Go back in thread:
Posted by Rick on June 10, 2000, at 16:20:28
In reply to Provigil poop out; klonopin counteracts provigil?, posted by S.D. on June 9, 2000, at 17:14:11
You're right, SD, this is certainly one for the neurology/psychopharmacology experts to chime in on. But at this stage, rat brain GABA-inhibition studies can provide nothing more than theoretical food for thought on the possible clinical effect of adding Provigil in Klonopin-treated human Social Phobia.
There are just so many factors to consider that I cannot even begin to enumerate them (and I'm sure there are even far more considerations that the experts could cite). But here are just a few of the thoughts that come to mind (with the disclaimer that a few of my layman satements *might* reflect incomplete or even plain-wrong understanding of pharmocological or psychiatric issues):
-- GABA reactions to Provigil could be different in socially anxious rats, and certainly could be different in humans.
-- Several of the studies of the anti-GABA effects of Provigil varied from significant in some regions of the brain to nil (or requiring a much higher dose of Provigil) in others.
-- While similar in many ways, different benzos vary in strength and theraputic value. For instance, Klonopin is a high-potency benzo that has been proven very effective in Social Phobia, while Valium usually has no value at all in treating this form of anxiety. Moreover, Klonopin's unique effects in a variety of non-anxiety disorders such as epilepsy, restless leg syndrome, dystonia, and tremor, suggestions a pharmacology which may involve more than simple GABA agonism.
--If I was reading the studies correctly, the observed GABA-reduction with Provigil (and again, occuring only in selected site/dosage situations) maxed at 20%. (It was hard for me to understand the data as presented. I *believe* the 80% figure cited represented the amount of GABA *maintained* at those sites, but maybe it instead referred to GABA *reduction* levels.) A 20% maximum reduction would proably not have much clinical import, especially if other significant sites were unaffected.
-- For me, concurrent use of three C
Posted by Rick on June 10, 2000, at 16:32:05
In reply to Re: Provigil poop out; klonopin counteracts provigil?, posted by Rick on June 10, 2000, at 16:20:28
(I'm still having trouble getting everything to post at once, so here's more -- hopefully through the end):
-- For me, concurrent use of three CYP 450-metabolized drugs might be increasing the bioavailabily and clinical effect of some of them. A likely candidate this kind of potentiating effect would be the Klonopin, which would help offset any anti-GABA effects of Provigil. From everything I've read, Provigil shows little increase in benefit at dosages higher than the standard 200mg; while proportionally, bioavailabilty increases add to Klonopin's anxiolytic properties over a pretty wide range. Also, while not specifically tested, phrmacologists seem to widely believe that Serzone inhibits metabolism of Klonopin, and thus increases its blood levels. It has been demonstrated that Serzone doubles Xanax availability two-fold, and increases blood concentration of another benzo (was it triazolam?) so dramatically that concommitant (sp?) use is discouraged. Incidentally, the official Provigil monograph specifically cites studies that looked at its use with selected benzos, and does not report any watchouts for such a cobination While their focus was on safety of the combination (no problems found), I would suspect that loss of anxiolytic effect would have been led to a warning, contraindication, or suggestion to monitor benzo effectiveness and increase the benzo dosage if warranted. Finally, while new interactions are being uncovered for lots of psychoactive drugs every year (some of them beneficial), drug interaction sites such as Mayo Clinic, Drug Data Bank, and CVS show very few reported interactions with Provigil, and in particular none between Provigil and any benzo. While Provigil has only been in the U.S. about 18 months, France -- a country with heavy benzo usage -- has had over ten years to uncover interactions. (It would be interesting to see a French monograph for Provigil.)
-- To me, this is probably the best evidence of all that Provigil doesn't kill the ef
Posted by Rick on June 10, 2000, at 16:42:37
In reply to More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:32:05
(Let's continue, shall we?)
--To me, this is probably the best evidence of all that Provigil doesn't kill the effects of Klonopin: When I take my small afternoon dose of Klonopin (0.25mg), I can really FEEL it, even more so than before I started the Provigil. The two meds feel like they are *complementing* each other by treating different components of my Social Phobia.
Anyways, those are just a few of my thoughts regarding the possibility of Klonopin and Proigil working at cross-purposes. Theory and narrowly-focused, vaguely-suggestive rat-brain studies aside, for me the bottom line is that everything other treatment I've tried has paled beside this combo. (Although I should reiterate that 1.5-2.0 mg Klonopin alone helped me an awful lot. What I'm doing now is "going for the gold".)
I'm thrilled with my Social Phobia cocktail of Serzone, Klonopin, and Provigil.Rick
-----> >I just hope what some have said about a tendency
> >for Provigil to poop out doesn't surface for me.
> >
> Maybe some of our resident pharmacology/neurochemistry experts can help out, but aren't Klonopin and Provigil kind of opposite? (Klonopin increasing GABA(†) and Provigil (modafinil) decreasing it(‡) ). Does this suggest any danger besides the two possibly counteracting each other's effect to some extent?
>
> † sorry, no ref. for this but I believe it's right
>
> ‡ "The effects of modafinil on glutamatergic and GABAergic transmission in the rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA and PH."
> - from (according to http://www.modafinil.com/glutam.html):
> "The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade"
> by
> Ferraro L, Antonelli T, Tanganelli S, O'Connor WT,
> Perez de la Mora M, Mendez-Franc
Posted by michael on June 10, 2000, at 17:22:46
In reply to More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:32:05
Rick:(It would be interesting to see a French monograph for Provigil.)
>
http://www2.biam2.org/www/Sub4900.htmlVoila:
MODAFINIL
Introduction dans BIAM : 8/2/1993
Dernière mise à jour : 10/4/2000
Etat : validéeIdentification de la substance
Propriétés Pharmacologiques
Mécanismes d'action
Effets Recherchés
Indications thérapeutiques
Effets secondaires
Effets sur la descendance
Pharmaco-Dépendance
Précautions d'emploi
Contre-Indications
Voies d'administration
Posologie & mode d'administration
Pharmaco-Cinétique
Bibliographie
Spécialités contenant la substance
Identification de la substance
Formule Chimique :
[(Diphénylméthyl)sulfinyl]-2 acétamideEnsemble des dénominations
CAS : 68693-11-8
DCIR : MODAFINIL
bordereau : 2973 code expérimentation : CRL-40476
rINN : MODAFINIL
Regime : liste I
Remarque sur le regime : JO 20/09/92Proprietés Pharmacologiques
PSYCHOSTIMULANT (principale certaine)
Mécanismes d'actionprincipal
Substance éveillante de mécanisme différent des amphétamines. Son activité serait liée à l'activation de la transmission alpha adrénergique au niveau central par un mécanisme qui reste à préciser.
L'activité pourrait être due à une réduction de l'activité gabaergique corticale consécutive à une activation noradrénergique et sérotoninergique :
- Eur J Pharmacol 1995;273:63-71.
Effets RecherchésPSYCHOSTIMULANT (principal)
Indications ThérapeutiquesNARCOLEPSIE (principale)
Référence :
- Lettre du Pharmacologue 1995;9:3-42.
Etude positive sur 283 patients traités pendant 9 semaines:
- Ann Neurol 1998;43:88-97.
Etude multicentrique sur 283 patients traités 9 semaines; résultats positifs:
- Ann Neurol 1998;43:88-97.HYPERSOMNIE (principale)
Hypersomnie idiopathique.
Diminue la somnolence diurne associée aux apnées du sommeil.SYNDROME DE GELINEAU (principale)
Agit sur la composant narcoleptique du syndrome de Gélineau :
- Lettre du Pharmacologue 1995;9:3-42.
Effets secondairesEXCITATION PSYCHOMOTRICE (CERTAIN RARE)
Episodes d'excitation.INSOMNIE (CERTAIN RARE)
ANOREXIE (CERTAIN RARE)
NAUSEE (CERTAIN RARE)
SIALORRHEE (CERTAIN RARE)
DOULEUR EPIGASTRIQUE (CERTAIN RARE)
CEPHALEE (CERTAIN RARE)
ERUPTION CUTANEE (CERTAIN TRES RARE)
DYSKINESIE BUCCOFACIALE (CERTAIN TRES RARE)
TACHYCARDIE (CERTAIN TRES RARE)
Tachycardie modérée.
Effets sur la descendanceNON TERATOGENE CHEZ L'ANIMAL
Etude réalisée chez le rat, le lapin.INFORMATION MANQUANTE DANS L'ESPECE HUMAINE
Pharmaco-DépendanceNON
A ce jour, la non existence d'un potentiel de pharmacodépendance du modafinil n'a pas été nettement établie :
- Aviat Space Environ Med 1991;62:432-435.
Précautions d'emploiSPORTIFS
Substance interdite :
- Journal Officiel du 7 Mars 2000.INSUFFISANCE CORONARIENNE
TROUBLE DU RYTHME VENTRICULAIRE
INSUFFISANCE HEPATOCELLULAIRE GRAVE
Réduire la posologie de moitié.
Contre-IndicationsANXIETE
Anxiété majeure.GROSSESSE
Information manquante.ALLAITEMENT
Information manquante.
Voies d'administration
- 1 - ORALEPosologie et mode d'administration
Doses usuelles par voie orale :
Adultes : deux cents à quatre cents milligrammes par jour (200 à 400 mg/j) en deux prises, matin et soir.
Pharmaco-Cinétique
- 1 - REPARTITION 62 % lien protéines plasmatiques
- 2 - DEMI VIE 10 à 13 heure(s)
- 3 - ELIMINATION voie rénaleAbsorption
Résorption lente.
Pic plasmatique voisin de 3,7 mg/l après une prise orale de de 200 mg.
La biodisponibilité n'est pas modifiée par la prise d'aliments.
Le pic plasmatique est retardé et la biodisponibilité est doublée en cas d'insuffisance hépatique.
Répartition
Liaison aux protéines plasmatiques : 62%.
Demi-Vie
La demi-vie se situe entre 10 et 13 heures .
Les demi-vies d'élimination sont indépendantes de la dose administrée pour des doses comprises entre 50 et 400 mg.
La demi-vie est doublée chez l'insuffisant rénal ou hépatique.
Métabolisme
Le modafinil est métabolisé par le foie en modafinil acide et modafinil sulfone.
Elimination
(VOIE RENALE)
Principalement éliminé dans les urines sous forme de modafinil acide. Environ 10% de la dose administrée sont éliminés sous forme inchangée.
Bibliographie
- Dossier d'Information Médicale et Pharmaceutique du produit MODIODAL- 1994, Laboratoire LAFON. (CREATION)
Spécialités
Principe actif présent en constituant unique dans les spécialités françaises suivantes :
MODIODAL 100 mg comprimés
Principe actif présent en constituant unique dans les spécialités étrangères suivantes :
PROVIGIL (GRANDE-BRETAGNE)
Associations avec des substances
A SURVEILLER :CICLOSPORINE
CLOMIPRAMINE CHLORHYDRATE
Posted by michael on June 10, 2000, at 17:35:50
In reply to More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:32:05
(It would be interesting to see a French monograph for Provigil.)
>
The french one's difficult to read - this one is from a brittish db. It appears they've been using it at least since 1997, possibly longer...Cephalon UK Limited
11/13 Frederick Sanger Road
Surrey Research Park
Guildford GU2 5YD
Telephone: 01483 453360 Facsimile: 01483 453324
PROVIGIL TM
Qualitative and quantitative composition
Modafinil 100 mg per tablet.Pharmaceutical form
Tablets.Clinical particulars
Therapeutic indications: Narcolepsy.
Posology and Method of Administration:Adults: The recommended daily dose is 200-400 mg. PROVIGIL may be taken as two divided doses in the morning and at noon, or as a single dose in the morning according to physician assessment of the patient and the patient's response.
Elderly: There are limited data available on the use of PROVIGIL in elderly patients. In view of lower clearance and increased AUC, it is recommended that patients over 65 years of age should commence therapy at 100 mg daily. The maximum dose of 400 mg per day should only be used in the absence of renal or hepatic impairment.
Hepatic and renal failure: The dose in patients with severe hepatic or renal failure should be reduced by half (100-200 mg/day).
Children: See Contra-indications.
Contra-indications: PROVIGIL is contra-indicated for use during pregnancy and lactation, in children, moderate to severe hypertension, and arrhythmia. Known hypersensitivity to PROVIGIL or any component of the preparation.
Special warnings and special precautions for use: Patients with major anxiety should only receive treatment with PROVIGIL in a specialist unit.
Sexually active women of child-bearing potential should be established on a contraceptive programme before taking PROVIGIL.
Blood pressure and heart rate should be monitored in hypertensive patients.
It is recommended that PROVIGIL tablets not be used in patients with a history of left ventricular hypertrophy or ischaemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with CNS stimulant use.
Whilst studies with modafinil have demonstrated a low potential for dependence, as with other psychoactive agents, the possibility of dependence with long term use cannot be entirely excluded.
Interactions with other medicaments and other forms of interaction:
Oral contraceptives: The effectiveness of oral contraceptives may be impaired due to enzyme induction activity of PROVIGIL. When oral contraceptives are used, a product containing 50 micrograms or more of ethinyl oestradiol should be taken. Adequate contraception will require continuation of the oral contraceptive for two cycles after stopping PROVIGIL.
Tricyclic antidepressants: In a single dose pharmacokinetic interaction study of PROVIGIL (200 mg) and clomipramine (50 mg), no clinically important alterations in the pharmacokinetic profile of PROVIGIL or clomipramine were noted, however, patients receiving such medication should be carefully monitored.
Anti-convulsant therapy: In view of the enzyme inducing potential of PROVIGIL, care should be observed with co-administration of these drugs.
Pregnancy and lactation: Modafinil has been shown to be non-teratogenic in preclinical reproductive toxicology investigations at doses greater than the maximum clinical dose. However, blood levels in preclinical safety studies, due to metabolic autoinduction, were less than or similar to that expected in patients. As there have been no adequate or well controlled studies of modafinil in pregnant women, PROVIGIL should be contra-indicated for use in pregnancy and lactation.
Effects on ability to drive and use machines: There is no information available concerning the effects of PROVIGIL on vehicle driving and/or the ability to use machinery.
Undesirable effects: Episodes of feelings of nervousness, excitation, aggressive tendencies, insomnia, personality disorder, anorexia, headache, CNS stimulation, euphoria, abdominal pain, dry mouth, palpitation, tachycardia, hypertension, and tremor have been reported.
Gastrointestinal disturbances (nausea, gastric discomfort) have been reported in clinical trials, usually regressing when tablets are taken during meals. There have also been reports of pruritic skin rashes and, very rarely, cases of buccofacial dyskinesia.
A dose related increase in alkaline phosphatase has been observed.
The safety of PROVIGIL has not been studied beyond 40 weeks of continuous use.
Overdose: The chief symptom following massive ingestion is insomnia.
Management: Induced emesis or gastric lavage should be considered. Hospitalisation and surveillance of psychomotor status; cardiovascular monitoring or surveillance until the patient's symptoms have resolved.
Pharmacological properties
Pharmacodynamic properties: Modafinil promotes wakefulness in a variety of species, including man. The precise mechanism(s) through which modafinil promotes wakefulness is unknown, although the wake-promoting effects of modafinil can be attenuated by alpha-adrenergic antagonists.
Modafinil in man restores and/or improves the level of wakefulness and daytime alertness in relation to the dose administered. Starting from the dose of 100 mg in the morning, changes are found in electrophysiological parameters reflecting alertness (ratio of power of alpha rhythm to power of ;gq rhythm). Starting from 200 mg in the morning, an increase is seen in latency periods in the multiple sleep latency test. It opposes the impairment of cognitive (memory in particular), psychomotor and neurosensorial performances induced by sleep deprivation. This activity is obtained in the absence of any modifications concerning behaviour, appetite and habituation.Morning administration of 200 mg does not appear to affect nocturnal sleep. Administration of 100 mg morning and noon may prolong the subjective time taken to fall asleep. Evening administration may disturb sleep. This pharmacodynamic activity does not appear to affect the autonomic nervous system.
Pharmacokinetic properties: The pharmacokinetics of modafinil are linear and independent of the dose administered. Absorption of modafinil following oral administration is good but slow. Peak plasma concentration is reached two to three hours after ingestion. Amounts absorbed increase in proportion to doses administered.
Modafinil is moderately bound to plasma proteins (62%), essentially to albumin. This degree of protein binding is such that the risk of interaction with strongly bound drugs is unlikely.
Modafinil is metabolised by the liver. The chief metabolite (40-50% of the dose), acid modafinil, has no pharmacological activity. The excretion of modafinil and its metabolites is chiefly renal, with a small proportion being eliminated unchanged (< 10%).
The elimination half-life of modafinil is long (10-12 hours) and enables a treatment regimen based upon one or two doses/day.
Preclinical safety data: Toxicology studies by single and repeated dosing have revealed no particular toxic action in animals.
Reproduction function studies have revealed no effect on fertility, nor any teratogenic effect, nor any effect on viability, growth or development of the offspring.
This drug is not considered to be mutagenic or carcinogenic.
Animal exposure to modafinil, based on actual blood levels in the general toxicology, reproductive and carcinogenicity studies, was less than or similar to that expected in humans. This circumstance is the result of metabolic auto-induction noted in the preclinical studies. However, animal exposure on a mg/kg dose basis to modafinil in the general toxicology, reproductive and carcinogenicity studies was greater than the expected exposure, calculated on a similar basis, in humans.
Pharmaceutical particulars
List of excipients: Lactose monohydrate, corn starch, magnesium silicate, croscarmellose sodium, povidone K90, talc and magnesium stearate.
Incompatibilities: None knownShelf life: Three years
Special precautions for storage: Store at less than 25°C in a dry place. Protect from direct heat and sunlight.
Nature and contents of container: 30 tablets in PVC/PE/Aclar/Aluminium blister
60 tablets in PVC/PE/Aclar/Aluminium blister
90 tablets in PVC/PE/Aclar/Aluminium blister
Instructions for use/handling: Not applicable.
Marketing authorisation number
PL 16260/0001Date of first authorisation/renewal of authorisation
14 October 1997Date of (partial) revision of text
22 June 1998
Posted by Rick on June 10, 2000, at 20:06:04
In reply to how about a brittish monograph? » Rick, posted by michael on June 10, 2000, at 17:35:50
Thanks for the European monograhps on modafinil, Michael.
I ran the French monograph (the original, not your copy) through Alta-Vista translation, and it turned out to say pretty much the same thing as the British one.
Wow, I never realized how much more thorough U.S. monograhps are! Maybe that's reflective of the amount of testing that's required before the FDA will approve a drug.
None of the monographs discourage combination benzo/Provigil use. In fact, the U.S. monograph has references to Provigil use with triazolam (no safety issues found) and diazepam. It says that Provigil may increase blood levels of diazepam (and other drugs which share Provigil's elimination mechanisms), thus calling for possible diazepam dosage reduction.
There are no absolute contraindications given at all in the U.S. monograph, except for known hyper-sensitivity to the drug. In terms of worsening of CNS-related disorders, the only problem seen was in one patient with a history of psychosis.
The French and British mongraphs, but not the U.S.'s -- warn against prescribing Provigil to patients with moderate-to-severe hypertension (BTW, it hasn't affected my blood pressure). The European, but not the American, guidelines also say that Provigil should be prescribed to patients with "Major Anxiety" only by a "specialist" (I assume this means a psychiatrist instead of a general practitioner.) I think that's prudent advice, but needn't be an "absolute". General practitioners often seem pretty much in the dark about depression, but they can be even more clueless when it comes to anxiety disordes like Panic, GAD, OCD. and Social Phobia. "Fun Fact": Did you know that in England the first-line medication for GENERALIZED Social Phobia is beta blockers??!!
Posted by SLS on June 11, 2000, at 10:27:50
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:42:37
What are the current thoughts regarding the role of NE alpha-1 agonism in the wakefulness-promoting properties of Provigil?
> -- While similar in many ways, different benzos vary in strength and theraputic value. For instance, Klonopin is a high-potency benzo that has been proven very effective in Social Phobia, while Valium usually has no value at all in treating this form of anxiety. Moreover, Klonopin's unique effects in a variety of non-anxiety disorders such as epilepsy, restless leg syndrome, dystonia, and tremor, suggestions a pharmacology which may involve more than simple GABA agonism.
As far as the varied effects of the benzodiazepines are concerned, one factor underlying them may be that there are different subtypes of benzo-receptors to which they bind with varying affinities. In addition, I recall that Klonopin (clonazepam) was thought to have serotonergic properties.
> --If I was reading the studies correctly, the observed GABA-reduction with Provigil (and again, occuring only in selected site/dosage situations) maxed at 20%. (It was hard for me to understand the data as presented. I *believe* the 80% figure cited represented the amount of GABA *maintained* at those sites, but maybe it instead referred to GABA *reduction* levels.) A 20% maximum reduction would proably not have much clinical import, especially if other significant sites were unaffected.
I think 20% may be a pretty big number under certain conditions. Just think what a difference a 20% change in the dosage of a drug can make.
As you have mentioned, an important variable that is sometimes overlooked when attempting to understand the differing effects of drugs and neurotransmitters is in which locations or structures within the brain they accumulate and act.
From what I was able to glean from abstracts, despite my misspelling in the thread below, Provigil increases the extracellular concentration of glutamate in the hippocampus and thalamus. I believe it is this increase in glutamate that is responsible for the inhibition of GABAergic neurons there. Perhaps it is the inhibition of efferent GABAergic pathways that is responsible for the increased release of dopamine in the nucleus accumbens observed with Provigil. This may account for some of its psychostimulant effects - motivation, vigilance, reward-seeking, euphoria. Provigil also has been reported to increase the release of glutamate in the hypothalamus. Through similar mechanisms, this may be what is responsible for its ability to produce anxiety and activation. I don't know what the observed increased release of glutamate in the cerebral cortex is all about.
How would you compare modafinil and adrafinil in the treatment of depression? Is there a trend towards greater "poop-out" with modafinil?
What sorts of effects does adrafinil have on the liver, and what is the rate of occurrence?
- Scott
Posted by Rick on June 11, 2000, at 16:49:29
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by SLS on June 11, 2000, at 10:27:50
(NOTE: Given the posting difficulties I've had recently, this post may end up getting cut-off in the middle. If so, I will post the second half in a follow-up message)
Scott -
You clearly have a deeper knowledge of pharmocology than I do. I found your observations very interesting.
I've never used adrafinil, and have little knowledge about it other than what I've read here on Psycho-Babble and the smart-drug sites. What I do know is that in France, quarterly liver-function tests are now required for adrafinil users because there have been some cases of significant hepatic toxicity. Modafinil (Provigil) does not share this requirement.
From what I've read recently, Provigil's mechanisms are still mostly a mystery. It is still usually referred to as an adrenergic drug, although a recent review from U.S. Pharmicist says that the original theory of direct or indirect NE alpha-1 agonism has fallen out of favor. Nonetheless, it appears that that Provigil won't promote wakefulness unless the alpha-adrenergic system is functioning properly. As for poop-out, again I can't speak to adrafinil, but as was noted earlier in the thread, poop-out reports reflect Provigil's tendency to sometimes start self-inducing production of metabolizing enzymes. The manufacturer says that this be corrected by a modest (and temporary?) dosage increase. I saw one nine-month study that showed sustained effectiveness (at a constant dose) for all responders.
The following from Lexi-Com seems to sum up the current theories pretty well, incuding the possibility of GABA reduction effects at certain sites:
"The exact mechanism of action is unclear, it does not appear to alter the release of dopamine or norepinephrine, it may exert its stimulant effects by decreasing GABA-mediated neurotransmission, although this theory has not yet been fully evaluated; several studies also suggest that an intact central alpha-adrenergic system is required for modafinil's activity; the drug increases high-frequ
Posted by Rick on June 11, 2000, at 17:02:22
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 11, 2000, at 16:49:29
(As anticipated, my response to Scott was cut off midway. Continuing...)
"The exact mechanism of action is unclear, it does not appear to alter the release of dopamine or norepinephrine, it may exert its stimulant effects by decreasing GABA-mediated neurotransmission, although this theory has not yet been fully evaluated; several studies also suggest that an intact central alpha-adrenergic system is required for modafinil's activity; the drug increases high-frequency alpha waves while decreasing both delta and theta wave activity, and these effects are consistent with generalized increases in mental alertness."
Finally, I just ran across an interesting new Medline abstract of a small study of Provigil augmentation of antidepressants. I'll post that separately.
Rick
> What are the current thoughts regarding the role of NE alpha-1 agonism in the wakefulness-promoting properties of Provigil?
>
> > -- While similar in many ways, different benzos vary in strength and theraputic value. For instance, Klonopin is a high-potency benzo that has been proven very effective in Social Phobia, while Valium usually has no value at all in treating this form of anxiety. Moreover, Klonopin's unique effects in a variety of non-anxiety disorders such as epilepsy, restless leg syndrome, dystonia, and tremor, suggestions a pharmacology which may involve more than simple GABA agonism.
>
> As far as the varied effects of the benzodiazepines are concerned, one factor underlying them may be that there are different subtypes of benzo-receptors to which they bind with varying affinities. In addition, I recall that Klonopin (clonazepam) was thought to have serotonergic properties.
>
> > --If I was reading the studies correctly, the observed GABA-reduction with Provigil (and again, occuring only in selected site/dosage situations) maxed at 20%. (It was hard for me to understand the data as presented. I *believe* the 80% figure cited represented the amount of GABA *maintained* at those
Posted by Aimee on September 21, 2000, at 18:55:39
In reply to Social Phobia Cocktail -- WOW!!!, posted by Rick on June 8, 2000, at 0:50:53
Bless you, Rick! Thank you so much for detailing
your experiences with the various medications and
for coming up with your amazing cocktail.
My question for you is, do you take a generic form
of Klonopin or the original?Take Care,
Aimee
> Hope it's not too good to last:
>
> Klonopin (1 mg morning, .25 mg afternoon)
> Serzone (150 mg morning, 150 mg evening)
> Provigil (200 mg morning)
>
> (Since these meds plus the Prilosec I'm taking are metabolized largely through the same liver enzymes, bioavailability may be increased for some of them...thus keeping my dosage requirements somewhat lower than usual.)
>
> Klonopin's been great all along, but I've been looking for an even higher level of improvement. Everthing else I've tried, either before or since starting Klonopin, has failed to provide enhancement and/or has caused non-abating bothersome side effects.
>
> The Provigil is incredible, at least for me. I was afraid it would cause counter-productive nervousness, especially when I upped the daily dose from 100 mg to the 200 mg generally recommended for the med's official narcolepsy indication. But instead, the Provigil consistently provides a great "non-wired" wakefulness (although with NO problem sleeping when I WANT to); enhances energy, motivation and cognition; and makes me more assertive and a lot more sociable. I just hope what some have said about a tendency for Provigil to poop out doesn't surface for me.
>
> For the record, I've been taking Klonopin about ten months (but less now than previously); Serzone for about four weeks (added it to Celexa, then soon dumped the Celexa); and Provigil for about three weeks.
>
> Just wanted to share a success story regarding treatment of my non-depressive Social Anxiety. Who knows if it will last? But so far *every* day for the last two weeks has been just wondeful -- morning to afternnon to night to snooze-land. And as good as everything is now, things seem to be headed nowhere but up.
>
> Rick
Posted by Rick on September 22, 2000, at 2:18:23
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by Aimee on September 21, 2000, at 18:55:39
Aimee -
You're quite welcome! Am I correct in assuming that this is a combo you're considering, rather than currently taking?
While I'm usually fairly open to generics, I've heard so many users comment on a lower/variable potency for generic clonazepam that I've stuck with .5 mg (orange) branded Klonopin from the start. If you end up needing to split a .5 as I do, I suggest getting a good pill splitter. They're rather delicate, despite the scoring. Provigil 200 mg tabs, on the other hand, are pretty easy to simply break in half by hand along the score. (As I will discuss, I now typically need only 100 mg. Provigil to get the full benefits.)
Assuming you haven't started yet, I think there's a great chance you will enjoy the same luck I have had with this combo. Unless you're clinically depressed, I would take the Klonopin alone for the first two-four weeks, so that you can feel out what it does for you and how much you need, while ramping up to a full dose and working through any early sedation. (In a benzo/AD combination, why is the benzo the med always assumed to be causing sedation??) After the Klonopin calms your anxiety, then you can add the Serzone and Provigil together. (I started the Serzone first, but the Provigil seems to have "jump-started" it... and replaced some minor fatigue with major motivation and cognitive benefit.)
If you do have major depression, you might need to try any of several different approaches that could includie starting all three at once (although perhaps a little unorthodox and less analyzable). You'll have to work with your pdoc. But don't worry, even if the timing/sequencing causes some bumps along the way, you'll get there.
Over the last few months, I've stabilized on 1.25 mg/day of Klonopin (1.00 upon awakening, and .25 early afternoon; 450 mg/day Serzone (300 upon awakening, and 150 early afternoon); and 100 mg/day of Provigil when I get up. Once in awhile, for a day or two, I'll take an extra 100 mg. of Provigil at noon or just a little later. (I've always found that 200 mg doses of Provigil work better when staggered this way. You should avoid taking any less than ten hours before bedtime.)
If this cocktail IS "too good to last", I haven't seen any signs of poop-out yet!:
I've just been attending a big company convention at an out-of-town resort -- same locale as two years ago (pre-meds) -- and the difference in how I feel and behave is incredible. I can't believe this calm but highly participatory individual (me) is the same person who's heart felt as if it was going to jump out of my chest just at the *thought* of speaking up last time I was here. When especially challenging situations are coming up, I sometimes take up to .5 mg extra Klonopin. As it turns out, I took .25 mg extra (before our "gala supper") yesterday, and didn't feel the need to take any extra today.Good Luck!
Rick
> Bless you, Rick! Thank you so much for detailing
> your experiences with the various medications and
> for coming up with your amazing cocktail.
> My question for you is, do you take a generic form
> of Klonopin or the original?
>
> Take Care,
> Aimee
>
>
>
>
>
>
> > Hope it's not too good to last:
> >
> > Klonopin (1 mg morning, .25 mg afternoon)
> > Serzone (150 mg morning, 150 mg evening)
> > Provigil (200 mg morning)
> >
> > (Since these meds plus the Prilosec I'm taking are metabolized largely through the same liver enzymes, bioavailability may be increased for some of them...thus keeping my dosage requirements somewhat lower than usual.)
> >
> > Klonopin's been great all along, but I've been looking for an even higher level of improvement. Everthing else I've tried, either before or since starting Klonopin, has failed to provide enhancement and/or has caused non-abating bothersome side effects.
> >
> > The Provigil is incredible, at least for me. I was afraid it would cause counter-productive nervousness, especially when I upped the daily dose from 100 mg to the 200 mg generally recommended for the med's official narcolepsy indication. But instead, the Provigil consistently provides a great "non-wired" wakefulness (although with NO problem sleeping when I WANT to); enhances energy, motivation and cognition; and makes me more assertive and a lot more sociable. I just hope what some have said about a tendency for Provigil to poop out doesn't surface for me.
> >
> > For the record, I've been taking Klonopin about ten months (but less now than previously); Serzone for about four weeks (added it to Celexa, then soon dumped the Celexa); and Provigil for about three weeks.
> >
> > Just wanted to share a success story regarding treatment of my non-depressive Social Anxiety. Who knows if it will last? But so far *every* day for the last two weeks has been just wondeful -- morning to afternnon to night to snooze-land. And as good as everything is now, things seem to be headed nowhere but up.
> >
> > Rick
Posted by Billb on September 22, 2000, at 16:16:25
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by AndrewB on June 8, 2000, at 21:06:26
These sound like exciting and promising cocktail combinations. Am I the only one who has a Pdoc who is not open to suggestions and is very non-agressive in trying new meds? At my present rate, it would take my Pdoc years to agree to evolve thru trials of these meds. What I currently get when I meet with him every three months is, "if it doesn't improve soon I'll up your paxil again."
Any tips on how to state my desires to my Pdoc to trial differnt meds. so that I can quickly identify a cocktail that works for me? Or is finding a new Pdoc the only solution. For me, that would mean driving out of this small town to an urban area.
By the way, thanks for the great posts!
Posted by Rick on September 23, 2000, at 3:21:26
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by Billb on September 22, 2000, at 16:16:25
> These sound like exciting and promising cocktail combinations. Am I the only one who has a Pdoc who is not open to suggestions and is very non-agressive in trying new meds? At my present rate, it would take my Pdoc years to agree to evolve thru trials of these meds. What I currently get when I meet with him every three months is, "if it doesn't improve soon I'll up your paxil again."
>
> Any tips on how to state my desires to my Pdoc to trial differnt meds. so that I can quickly identify a cocktail that works for me? Or is finding a new Pdoc the only solution. For me, that would mean driving out of this small town to an urban area.
>
> By the way, thanks for the great posts!That's a tough one to answer, since every pdoc's different. I'm still using my first one, who I picked out from the phone book, believe it or not. Even though he was expensive and out-of-network (i.e., lower insurance reimbursement), I was attracted by his listing which said "Phd, MD, 25 years experience" and "Psychobiologically Oriented, Psyhoanalytically Aware". I had done plenty of research, and I frankly wanted someone who I knew would be med-oriented and not bound by convention. (It turns out the "biological" part also involved a lot of dietary advice and an "insistence" that I lose at least 50 pounds, i.e., drop to 180. And as it turns out, his card says simply "psychoanalytically aware" -- what happened to "biological"?)
When he spent 3/4 of our second session explaining the history of the medication he was about to give me, and why it receives a bum rap, I knew I had probably selected the guy I wanted. The medication he gave me was Nardil, plus as-needed Xanax. I don't get the impression Social Anxiety treatment is really a specialty of his (even though the usually-avoided Nardil HAS proven to be the best AD for Social Phobia).
Frankly, he has about the worst "couchside" manner I could imagine, and is very conservative in some ways (including one GOOD one: the "start low, go slow" philosophy"). I saw him at least once a month (if the expense isn't a big difficulty, that may be one way for you to move thigs along more quickly). After "playing along" with several trials of drugs that made little sense for Social Phobia, I had a very troubling work experience, and went to him distraught that day (actually, I think I was overstating my anguish, but I WAS frustrated), and he gave me Tranxene (!). It was soon after this that I came back and politely but firmly said that nothing was working thus far, and that I wanted to try the Klonopin that I had read was so very effective for Social Phobia in placebo-based studies. He grudgingly said "O.K." (remember, this guy is no Social Phobia expert", and I was soon filled with delight that something was actually working -- WELL and QUICKLY -- and with no side effects except good ones (!) after the first week.
Since then, it's been mainly "stick with whatever works for you (Klonopin). Now, what have your dreams been lately". The other thing we've done in the last year is fine-tune. I've been pretty aggressive about what I wanted to add in an attempt to "go for the gold", although I certainly gave his ideas a try. Fortunately (but incorrectly, except perhaps for benzos), this guy expects patients to start showing response to a drug very quickly if its going to work, regardless of disorder. Thus, we could move on fairly quickly, after one or two quick dosage-adjustment attempts.
Our ideas on various Klonopin+ combos have ranged from very convergent to very divergent. I believe he was hoping I might be able to replace the Klonopin. It's NOT that he's benzophobic; he simply prefers AD's and other anti-anxiety drugs like BuSpar abd Neurontin. One thing that has worked in my favor, in addition to the frequent visits (that have become infrequent since I've found my powerful Anti-Social Phobia cocktail), is that I came armed with plenty of knowledge and research about the meds I wanted to try. It was hardest to get him to prescribe Provigil, which he had never used, and which he said had virtually no track record (True, in the U.S., anyways). But after I was looking for something to make more "up", and had failed trials of selegiline and Wellbutrin (with the Celexa I was taking then) due to increased anxiety, he wanted me to try Ritalin. I really didn't want Ritalin (he's a big fan), and kept talking to him about the supposedly gentler, non-addicting, and less side-effect-prone (NONE for me) stimulant Provigil. He had been intrigued by stories about the (French?) government giving soldiers Provigil in Desert Storm. But even as I pummelled him with research, and even as he was astounded that Caremark had sent outa notice advocating the use of this very-expensive drug over traditional amphetamine-based anti-narcoleptics, he was starting to write a prescription for Ritalin. But I kept insisting, and he said, "O.K., if you want to be the guinea pig, even though you're already doing pretty well...". I'm REALLY glad I prevailed there.
Sorry for getting carried away with the details of the story (actually, that was just a topline review!). Anyways, if you have to stick with the pdoc you have and you're not getting what you want, I would try to (1) Go as often as possible, and note your lack of any (good) response, especially after a dosage increase. (2) Inundate him with reputable research! If you want to try Klonopin, show him those Duke University abstracts I gave Donna Lynn the links to, addressing both high placebo-controlled efficacy, safety in long-term use and discontinuation, and continued effectiveness at maintenance doses. Better yet, obtain and print a copy of the complete journal articles. These are rigorous, reputable studies by Dr, Davidson of Duke, recognized in the psychiatric community as one of the nations pre-eminent Social Phobia experts. (Fyi, today Dr. Davidson goes along with the recommendation of an SSRI as the first-line treatment, even though none of the Paxil cntrolled studies have come anywhere near Klonopin's 78% response rate.) There are also studies available showing Serzone to be highly effective in Social Phobia, although they were not placebo controlled (3) Emphasize your continued mental (and side effect?) distres. If he's totally unresponsive, exaggerate or be more dramatic in your presentaton (4) Be politely pushy (of course, this became easier for me after I was aready on Klonopin!) (5) When push comes to shove, tell him/her that while you apreciate his/her efforts, you have researched other strategies, and that at this point you will have to look elsewhere, even if it means leaving town, and so you want to begin carefully weaning off the Paxil. (In the doc's defense, many patients do not see their biggest increase in AD anti-anxiety benfits until a full 8 to 12 weeks at a theraputic dose.) If you need to go back on Paxil, almost any GP will give it to you, although you might have to explain to them what Social Phobia is, and that Paxil has an FDA-approved indication for treatment of SP.
As for endorsing the foreign meds, I highly doubt your guy would go along. While I'm not too cofortable with the idea myself, you've seen that many on ths board seem to have had great success with legally-ordered (I think?) meds.
Good Luck,
Rick
Posted by MarkinBoston on September 25, 2000, at 22:51:36
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by Billb on September 22, 2000, at 16:16:25
>
> Any tips on how to state my desires to my Pdoc to trial differnt meds. so that I can quickly identify a cocktail that works for me? Or is finding a new Pdoc the only solution. For me, that would mean driving out of this small town to an urban area.After hearing people's problem's with doc's, I'm glad I have a good p-doc (a good endocrinologist is the opposite story). Over the last 8 years I've been seeing the same 50-something Dutch woman who believes in high doses for treatment resistant depressions like mine and is curious about papers I've read while also adding the clinical experience she and other doctors have at the psyc ward of a hospital where she also works some weekends. She knows I'm not suicidal, addictive, or stupid - so she will usually let me try what I want and may want to combine it with some suggestion. She had given me Klonipin at one time, but I couldn't really feel much effect from that for jitters caused by another anti-d (I forget which one now). This time, when I was really upset after withdrawing from the testosterone patch, I asked for diazapam because I was having some back soreness and Klonipin was just too weak for me. It did the trick, and I have a little extra on hand for when I need it. She is a little reluctant to try non-US drugs, as I havn't exhausted them all, but I may well working on JohnL's cocktail. She'll be ok with that, I'm sure.
Bottom line is that she's seen me for years, and in the past, only for major episodes. 9 months or a year would go by and I'd call her again once I start having trouble sleeping, thinking, and remembering. Otherwise, I'd been acceping of my dysthymia/anhedonia. So, that would make me non-drug seeking too. She's suggested I just stay on meds to prevent re-occurance of the major episodes, but I'm not willing to put up with the side effects full time. This time I told her my plan was to resolve the major episode and then concentrate on the dysthymia/anhedonia. Serzone as an anti-depressant taken at night is pretty free of side effects. Some dopamine agonist in the AM (Ritalin, adrafinil, modrafinil...) would then replace the Effexor XR which I dislike the side effects of sweating, anorgasmia, and apathy.
Now, if I could get an endrocrinologist to give me an estogen antagonist along with the testosterone suppliment I'd be joyous. Unfortunately, the best estrogen agonists are all FDA labeled as breast cancer drugs.
Posted by JohnB on September 25, 2000, at 23:17:09
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by Billb on September 22, 2000, at 16:16:25
Bill,
I think Rick's post is great advice and very informative. It's certainly worth a try. I would pose a different variation: Drive to the city. For this reason: Time is passing. You are not getting any younger my friend. Your pdoc sounds like he has all the time in the world. Do you?
Posted by Aimee on September 27, 2000, at 12:27:12
In reply to Social Phobia Cocktail -- WOW!!!, posted by Rick on June 8, 2000, at 0:50:53
Hi, Rick,
I researched Provigil and found that unfortunately
it can decrease the effectiveness of certain
contraceptives including birth control pills, and
implantable contraceptives. So i was wondering
if you think Effexor could be a substitute for
Provigil for helping with lack of energy?
Or if you have any other suggestions, as i really
value your opinion.Thanks,
Aimee> Hope it's not too good to last:
>
> Klonopin (1 mg morning, .25 mg afternoon)
> Serzone (150 mg morning, 150 mg evening)
> Provigil (200 mg morning)
>
> (Since these meds plus the Prilosec I'm taking are metabolized largely through the same liver enzymes, bioavailability may be increased for some of them...thus keeping my dosage requirements somewhat lower than usual.)
>
> Klonopin's been great all along, but I've been looking for an even higher level of improvement. Everthing else I've tried, either before or since starting Klonopin, has failed to provide enhancement and/or has caused non-abating bothersome side effects.
>
> The Provigil is incredible, at least for me. I was afraid it would cause counter-productive nervousness, especially when I upped the daily dose from 100 mg to the 200 mg generally recommended for the med's official narcolepsy indication. But instead, the Provigil consistently provides a great "non-wired" wakefulness (although with NO problem sleeping when I WANT to); enhances energy, motivation and cognition; and makes me more assertive and a lot more sociable. I just hope what some have said about a tendency for Provigil to poop out doesn't surface for me.
>
> For the record, I've been taking Klonopin about ten months (but less now than previously); Serzone for about four weeks (added it to Celexa, then soon dumped the Celexa); and Provigil for about three weeks.
>
> Just wanted to share a success story regarding treatment of my non-depressive Social Anxiety. Who knows if it will last? But so far *every* day for the last two weeks has been just wondeful -- morning to afternnon to night to snooze-land. And as good as everything is now, things seem to be headed nowhere but up.
>
> Rick
Posted by Rick on September 27, 2000, at 19:51:59
In reply to Re: Social Phobia Cocktail -- WOW!!! » Billb, posted by JohnB on September 25, 2000, at 23:17:09
> Bill,
> I think Rick's post is great advice and very informative. It's certainly worth a try. I would pose a different variation: Drive to the city. For this reason: Time is passing. You are not getting any younger my friend. Your pdoc sounds like he has all the time in the world. Do you?JohnB -
Your post speaks volumes with a few well-chosen words. Wish I could do that!
Rick
Posted by Rick on September 27, 2000, at 22:41:38
In reply to Re: Social Phobia Cocktail -- WOW!!!, posted by Aimee on September 27, 2000, at 12:27:12
Aimee --Sorry to hear that Provigil has the potential to render contraceptives ineffective. I wish I had a solid substitute recommendation for you, but I don't.
I've personally tried three stimulating meds. At one point I took selegiline with Klonopin (and pindolol), and it was very energizing, if not quite in the league of the Provigil. But it made me a bit edgy. I was taking a small dose (5 mg/day, which requires no food restrictions), but since then I've heard that as little as 2.5 mg/day, or 5 mg 2-3 times per week, can maintain the benfits after the first week. But since selegiline is a non-reversible MAOI, even small doses can have a minor, but real, potential for dangerous interaction with many prescription and non-prescription drugs (this does NOT include Klonopin, but it does include Serzone and SSRI's). So if you're not going to use an AD, low-dose selegiline might be worth trying. (Interestingly, the SSRI Celexa had an article on their website about how possible interactions -- specifically serotonin syndrome -- are rare and mild when combining low-dose selegiline with SSRI's. They said that this combo is routinely prescribed without complication to Parkinson's patients. Nonetheless, Celexa's own official monograph warns against combining any MAOI with Celexa!)
Wellbutrin is safe with Klonopin and Serzone, although the dosage should be pretty low and it should not be used if you have a history of seizures. But for me Wellbutrin was only slightly energizing, and added back a bit of anxiety. But again, it might work for you.
I have heard Effexor can be energizing for some, and sedating (especially at first) for others. And it has shown a lot of promise for Social Anxiety in a few open studies, reportedly with a unique anti-avoidance benefit -- especially for women. As for anecdotal reports, I've seen everything from "works great" to "no effect at all" for Effexor taken ALONE for Social Anxiety.
Other Babblers could probably give you more input on this one). I've never heard of a Serzone/Effexor combo, but as when combining any two serotonergic meds, there is some risk of serotonin syndrome. Nonetheless, such combos are often prescribed, with conservative doses and careful monitoring. Indeed, back when I was trying Celexa, my pdoc said that Effexor could possibly work to counter the Celexa-induced "dullness". But I've neve taken it.BTW, I don't know the potential effects of any of these meds on contraceptives.
Hope this helps.
Rick
Posted by Billb on October 1, 2000, at 14:12:58
In reply to Re: Social Phobia Cocktail -- WOW!!! » Aimee, posted by Rick on September 27, 2000, at 22:41:38
Thanks for the advice. What is the best way to find a pdoc who specializes in social anxiety and uses agressive strategies to identify the best medications to help my condition? Are there directories or references that will point me to a "good" pdoc?
The closest urban areas are Columbia SC, Charleston SC, Savannah GA, and Atlanta GA
Posted by JohnB on October 2, 2000, at 3:11:11
In reply to Re: Social Phobia Cocktail, Rick JohnB, posted by Billb on October 1, 2000, at 14:12:58
> Thanks for the advice. What is the best way to find a pdoc who specializes in social anxiety and uses agressive strategies to identify the best medications to help my condition? Are there directories or references that will point me to a "good" pdoc?
>
> The closest urban areas are Columbia SC, Charleston SC, Savannah GA, and Atlanta GABill:
1. Post your question as a new topic and someone may be able to help you.2. Try to get a referral thru a major university psych dept. (Duke Univ.?) or hospital in your area.
3. Be very clear on your first visit to any pdoc what your agenda is. If you get bad vibes from the person, move on. This saves loads of time.
Posted by rick_number1001@yahoo.com on August 17, 2001, at 1:43:07
In reply to More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:32:05
Interesting posts!
I am on a combo of 60 Nardil, 2.5 - 2.75 Klonopin
and 75-100 Provigil. Works very well.I recently put up the start of a website at the
encouragment and help of a friend.Please check it out and offer any input if you
want. It is at www.socialfear.comThanks for the posts.
BTW, I agree with a lot of the stuff I saw,
including Serzone reducing serotonin related
sexual side effects, I found it reduced Nardil
and Zoloft sexual side effects at certain doses.I believe Serzone is primarily an antagonist
of serotonin and norepinephrine.Anyway, signing out for now.
Posted by Rick on August 17, 2001, at 19:11:35
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by rick_number1001@yahoo.com on August 17, 2001, at 1:43:07
> Interesting posts!
>
> I am on a combo of 60 Nardil, 2.5 - 2.75 Klonopin
> and 75-100 Provigil. Works very well.
>
> I recently put up the start of a website at the
> encouragment and help of a friend.
>
> Please check it out and offer any input if you
> want. It is at www.socialfear.com
>
> Thanks for the posts.
>
> BTW, I agree with a lot of the stuff I saw,
> including Serzone reducing serotonin related
> sexual side effects, I found it reduced Nardil
> and Zoloft sexual side effects at certain doses.
>
> I believe Serzone is primarily an antagonist
> of serotonin and norepinephrine.
>
> Anyway, signing out for now.rick_number1001 -
Thanks for posting!
Finally, I find someone who has seen the anti-anxiety potential of the gentle stimulant Provigil! Getting pdocs (let alone GP's) to prescribe it is really tough, because they're unfamiliar with it and convinced it must *cause* anxiety. (I know that some Psycho-Babblers have ordered the related adrafinil from overseas for use in Social Phobia.)
I am always interested in hearing how Provigil works in tandem with various AD's, and was especially interested in hearing about a Nardil/Provigil combo. Apparently, it's effective!
BTW, I'm now at 1 mg Klonopin (occasionally 1.25 - 1.5); 300 mg Serzone (down again after having been up to 450 for quite awhile), and 100 mg Provigil (with an occasional "rejuvenating" spike to 200 for a day or two). Despite the lower Klonopin dosage, it's still the med I would stick with if I could only choose one. I believe drug interactions make my Klonopin blood levels more comparable to a somewhat higher dose. I've always insisted on branded Klonopin, but due to a recent mixup I ended up getting generic clonazepam a month ago (mf'd by Tiva -- their top-selling med), and it seems equivalent thus far. I don't like the fact that I'm usually left with some Klono-Dust when I split a generic pill, but that doesn't seem to have any theraputic significance.
Congratulations on putting together a GREAT website that succinctly but thoroughly -- and without the typical biases -- covers the keypoints of SP and its treatment. Some may quibble with some of the individual treatment recommendations, but there's lots there to help social phobics begin reclaiming their lives. I can really relate to your observations about how it's easier to remedy the "fear of people" than it is to reverse the simple inertia of ingrained, avoidance-generated social habits.
The only thing I might personally take issue with is the recommendation of considering caffeine when trying to treat an anxiety disorder. I had always found it hard to believe that caffeine could cause noticeably increased susceptibility to anxiety, but then discovered that it truly can have that effect, at least for me. I'm not saying caffeine reverses the medication benefit, but it does diminish it a bit, so I try to avoid it (or at least moderate my intake) on weekdays. Of course, some social phobic or otherwise anxious inividuals might be immune to caffeine-induced nervousness.
BTW, Nardil was the first psychotropic I was ever prescribed, and I quit it because the side effects were intolerable. Back then I had newly-identified high blood pressure (has since gone away, largely due to weight and anxiety reduction), but Nardil took it so far in the other direction that I was spontaneously falling down from dizziness -- in public areas, no less -- and ended up hitting my head more than once. I now realize that I upped my Nardil dosage too quickly despite my pdoc's cautions, and also realize that most of the side effects might have abated with time as you describe (maybe not the sexual dysfunction, though). While I know that the food restrictions are overstated (which is NOT to say "unimportant"!!), and I didn't find them terribly burdensome, the food-fanatic within is glad he doesn't have to adhere to any restrictions at all.
Speaking of Nardil and food, despite that med's reputation for causing big weight gain, I actually made my first successful (VERY successful, and sustained) attempt at weight loss while taking the MAOI. Again, YMMV.
BTW, I'm glad you wrote this before the "my-deja" e-mail service (and thus the address I had been listing here) is shut-down in a few months. Otherwise, I wouldn't have received Psycho-Babble's automatic e-mail alert about your update to this thread. (I only check back here occasionally, and don't look at the archives.)
Rick
Posted by rick_number1001@yahoo.com on August 18, 2001, at 3:46:24
In reply to Re: More:Provigil poop out;klono counteracts provigil? » rick_number1001@yahoo.com, posted by Rick on August 17, 2001, at 19:11:35
Thanks for the comments Rick!That was encouraging to hear and my
first feedback. I hadn't touched the site
for a couple months and just changed it a bit.Thanks for your own regimen info.
Can I ask how you rate your improvement on
your current regimen? (symtom wise anyway);
it sounds like we both sense a big difference
between symptom abatement and 'total remission'I have to admit I'm surprised (but pleased!)
that the regimen you currently take works so well,
only because it seems like there wouldn't be much
overall serotonin increase.In my case, Serzone and Klonopin both seem to
give me an anti-serotonin effect, such that either
one or both together will tend to cause a depression
in me that I don't have by nature (untreated). Both
of those meds also tend to reduce serotonin induced
sexual side effects in my case. Klonopin is
unquestionably pro-sexual in my case, and Serzone may
or may not be depending on dose and concurrent
medication.Provigil, on the other hand, does reported have
a pro-serotonin effect and I seem to sense some
serotonin (and dopamine) effect as well based on
it's effects.I did very well on Zoloft+Serzone+Klonopin
in the past except that laziness and sedation
were a bit problematic. I think that I probably
would do very well on Z50+S300+K2-4.5+P100-200.> Thanks for posting!
>
> Finally, I find someone who has seen the anti-anxiety potential of the gentle stimulant Provigil! Getting pdocs (let alone GP's) to prescribe it is really tough, because they're unfamiliar with it and convinced it must *cause* anxiety. (I know that some Psycho-Babblers have ordered the related adrafinil from overseas for use in Social Phobia.)
>
> I am always interested in hearing how Provigil works in tandem with various AD's, and was especially interested in hearing about a Nardil/Provigil combo. Apparently, it's effective!
>
> BTW, I'm now at 1 mg Klonopin (occasionally 1.25 - 1.5); 300 mg Serzone (down again after having been up to 450 for quite awhile), and 100 mg Provigil (with an occasional "rejuvenating" spike to 200 for a day or two). Despite the lower Klonopin dosage, it's still the med I would stick with if I could only choose one. I believe drug interactions make my Klonopin blood levels more comparable to a somewhat higher dose. I've always insisted on branded Klonopin, but due to a recent mixup I ended up getting generic clonazepam a month ago (mf'd by Tiva -- their top-selling med), and it seems equivalent thus far. I don't like the fact that I'm usually left with some Klono-Dust when I split a generic pill, but that doesn't seem to have any theraputic significance.
>
> Congratulations on putting together a GREAT website that succinctly but thoroughly -- and without the typical biases -- covers the keypoints of SP and its treatment. Some may quibble with some of the individual treatment recommendations, but there's lots there to help social phobics begin reclaiming their lives. I can really relate to your observations about how it's easier to remedy the "fear of people" than it is to reverse the simple inertia of ingrained, avoidance-generated social habits.
>
> The only thing I might personally take issue with is the recommendation of considering caffeine when trying to treat an anxiety disorder. I had always found it hard to believe that caffeine could cause noticeably increased susceptibility to anxiety, but then discovered that it truly can have that effect, at least for me. I'm not saying caffeine reverses the medication benefit, but it does diminish it a bit, so I try to avoid it (or at least moderate my intake) on weekdays. Of course, some social phobic or otherwise anxious inividuals might be immune to caffeine-induced nervousness.
>
> BTW, Nardil was the first psychotropic I was ever prescribed, and I quit it because the side effects were intolerable. Back then I had newly-identified high blood pressure (has since gone away, largely due to weight and anxiety reduction), but Nardil took it so far in the other direction that I was spontaneously falling down from dizziness -- in public areas, no less -- and ended up hitting my head more than once. I now realize that I upped my Nardil dosage too quickly despite my pdoc's cautions, and also realize that most of the side effects might have abated with time as you describe (maybe not the sexual dysfunction, though). While I know that the food restrictions are overstated (which is NOT to say "unimportant"!!), and I didn't find them terribly burdensome, the food-fanatic within is glad he doesn't have to adhere to any restrictions at all.
>
> Speaking of Nardil and food, despite that med's reputation for causing big weight gain, I actually made my first successful (VERY successful, and sustained) attempt at weight loss while taking the MAOI. Again, YMMV.
>
> BTW, I'm glad you wrote this before the "my-deja" e-mail service (and thus the address I had been listing here) is shut-down in a few months. Otherwise, I wouldn't have received Psycho-Babble's automatic e-mail alert about your update to this thread. (I only check back here occasionally, and don't look at the archives.)
>
> Rick
Posted by Rick on August 18, 2001, at 16:40:07
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by rick_number1001@yahoo.com on August 18, 2001, at 3:46:24
NOTE: THIS IS A LONG POST!
rick_number1001:
Symptom-wise -- which is my priority now that I’m middle-aged and in a stable relationship and career -- I’d say my improvement is about 80-85%, although for the past few weeks it feels more like 90-95% (more on that in a moment). For a slew of reasons, it’s hard to assess “overall” improvement, e.g. including the desire to seek a larger social network and get involved in outside-of-work social situations. There’s a complex mix of rational, irrational (but not psychologically abnormal), and lingering abnormal avoidant/compulsive tendencies that keep me from proactively seeking out social situations, and cause me to turn down invitations. The net result is that most of my fear of social situations has abated, as well as most of the anticipatory anxiety, but I still lean towards a desire to be with myself and those closest to me. Unlike before, though, when I do, say, have to go to a party I don’t worry about it in advance (although I may “resent” it), I’m comfortable when I’m there (a HUGE improvement), and I often end up really enjoying myself instead of dying to make my way to the door. Yet I’m still relieved (and pleased by how I handled it vs. the “old days”) when it’s over, because I can return to my greatest comfort zone.
Sorry about babbling, but that in itself is an indication of how “overall improvement” is hard for me to put a number on (anyone have a Liebowitz scale lying around?). Ironically, this ties in with a much-improved but still lingering SP-related factor: my concern – real or imagined -- that I often have trouble expressing myself.
Regardless, the botom line is that I’m thrilled with the amount of mental burden that has been lifted through my treatment, and the fact that I can really be “me” around other people instead of constantly worrying about what others think and suffering abnormal, troublesome physical and panic-like reactions. (Ironically, perhaps because of my OC tendencies which are still very much at play, when I’m in a previously-fear-inducing situation I sometimes spend an unreasonable amount of time marvelling at how well I’m handling them...kind of an ironic flip-flop of the excessive self-scrutinization that is part of social phobia.)
Believe me, if my current regimen wasn’t working so well, I wouldn’t still be taking the same three meds
after more than a year. Prior to that, I was on the meds merry-go-round so many of us have dealt with. I’ve experimented with timing and dosages, but that’s it.That last thought leads me to the even-futher increase in benefit “80% to 90%” that I’ve seen symptomatically in the last few weeks. I hesitated to bring this up for several reasons. One is that I sometimes go through periods where there is a little fluctuation in symptomatic relief, although I’m always far better off than before the combo. But usually these unexplained up-or-down blips last for hours-to-days, not weeks. Now it’s two weeks, and I haven’t experienced even that occasional, minor symptom (e.g., a slight tremor in my voice when I’m put on the spot and someone’s staring in my eyes waiting for me to respond). Another reason I hesitate is because I haven’t been taking the supplement I’m about to mention long enough to assess whether the effect will last. And I’m slightly concerned about safety, since this is not a well-known supplement in the US (it’s widely used in Europe and Japan for various indications). Indeed, I’ve always been skeptical of herbs and “fringe” supplements, and haven’t seen any benefit whatsoever in the past. (“Fringe” is an important word there – I take many supplemets and a multi-vitamin for physical and mental health benefit/protection, including B-Complex, Vit E, One-a-Day Over-50 – even though I’m NOT over 50 – alpha-lipoic acid, and more. It’s likely that in some way these -- and more importantly a few common prescription meds that interact with Serzone -- add to the effectiveness of my SP cocktail, as did weight-loss and caffeine reduction. Now, if I could only get ioff my lazy butt and exercise!)
This over-the-counter supplement is called VINPOCETINE. (I put it in caps in case you or other readers wanted to wade through my excessive babbling and cut to the chase.) It’s a mostly-synthetic derivitive of the Periwinkle plant. I’ve always been skeptical of herbally-based meds (in terms of effectiveness, safety, and product control), but I wanted to see if something might help with the mild memory impairment that is likely due to my meds. (Despite Klonopin’s reputation, some personal experimenting seemed to indicate that the memory impairment was attenuated when I stopped taking Serzone for awhile (but not surprisingly this made my SP treatment somewhat less robust). I also note that I saw no such memory loss until 6 months after adding Serzone and Provigil– after almost a year on a substantially larger dosage of Klonopin. As an aside, I saw one post where someone complained of memory deficit from Provigil , despite its purported memory-enhancing benefits...hmm).
Anyway, I *may* be seeing a litte memory benefit with Vinpocetine, but I’m not so sure. What I *have* noticed – even though this isn’t generally mentioned for this supplement – is added “fortification” of my already-strong Social Phobia cocktail. It seems to iron out the chinks that remain, add a smoothness and consistency. The purported cognitive benefit of Vinpocetine was originally (and sometimes still) thought to come from increased blood circulation and glucose utilization localized to the brain (vs. Ginkgo, which has a similar effect but throughout the whole body). Now the memory impact is thought to likely derive from neuronal protection.
What I’m seeing from Vinpocetine (Nature Made brand) is a simultaneously stimulating but calming effect, kind of like something that takes up where Provigil leaves off. I’m getting way out of my league here, but the American Journal of Psychiatry recentlt had an article detaining reduced blood flow in SP subjects vs. normal subjects when forced into a public speaking situation. SP’s started out with lower flow in many areas of the brain, and during the challenge SP cerebral blood flow actually dropped some, while there was a sahrp increase among normal subjects. While cause-vs.-effect isn’t clear, and I hardly understand all the nuances and might be drawing some overly-simplistic or plain-wrong conclusions, but is it possible Vinpocetine’s increased cerebral blood flow is compensating for an SP-induced decline that may accompany my “chink in the armor” moments? I also note that the med (it really *is* more of a drug than an herb) has been used in epilepsy, and there seems to be a strong overlap between meds that can be useful in epilepsy and social anxiety, e.g. Klonopin, Neurontin.
While there could be a placebo effect here, the mild-stimulation effect feels very real. And Vinpocetine is clearly doing *something* because I’ve had a 10-15 point drop in my blood glucose across the board. (I’m not diabetic – at least not “officially” -- but had one high reading during a test a few years ago. That’s when I started my diet and anxiety treatment, and I still monitor every few days. I’ve been normal to high-normal all along, but since staring Vinpocetine I’ve been in the low-normal range, which is the best place to be in most cases.) And maybe this is just by chance again, but for the last few weeks I’ve felt a lot more sexually charged, if you will (there was no dysfuntion before; I’m speaking of enhancement).
Perhaps most importantly, I’ve cut my Serzone back to 300 mg again, Klonopin to 1 mg, and haven’t felt the occasional need for a temporary boost in Provigil dose. AND...I’m now taking all of the psychotrpoics in the morning only (even though Serzone has a short half-life), while taking Vinpocetine three times a day. The ony exception was an extra .25 mg Klonopin before a party. It’s too early to judge, but right now I’m sticking with it. And if memory benefits DO kick in, that would be great – since that’s why I tried Vinpocetine in the first place! I seem to have a history of unexpected benefits from meds, especially Klonopin and Provigil. In fact, you are one of the few people besides myself that I’ve seen report sexual *enhancement* from Klonopin. Despite hundreds of references to Vinpocetine on Medline, I do wish I knew more about its long-term safety, and any “bad” interactions with other meds or supplements. In particular, there is “some evidence” that it has anticoagulant properties, which is probably good in general but I’d really like to keep taking my daily preventative baby aspirin yet I’m afraid of the risks associated with excessive blood-thinning.
But with all my gabbing about Vinpocetine, I don’t want to lose sight of the more important point. Namely, that after more than a year I’m still thrilled with the combo of Klonopin, Provigil and Serzone for non-depressive Social Phobia. Not the slightest indication of poop-out.
I’ve been warned that, “you WILL experience depression from Klonopin at some point.” And there have been occasional days that seemed pretty dark mentally (interestingly, this happened most recently when I had to go about five days without Provigil), but they pass quickly and I don’t think they really come close to clinical depression (if protracted, I guess they might qualify as dysthmia). In fact, largely due some lucky breaks in life, my Social Phobia has never led to clinical depression. There may have been one period where I could have had undiagnosed depression, during a period of deep grief exacerbated by a slew of factors surrounding my mother’s brain cancer that made it maximally shocking and difficult to deal with.
As for serotonergic effects, the studies I've seen generally conclude that Klonopin causes anything from a mild decrease to a mild increase in serotinin availability. Klonopin apparently DOES cause an inhibitory pre-synaptic seorotin release, but this effect is balance by other, pro-serotnergic effects. As for Serzone, it IS a serotenergic (and somewhhat adrenergic) medication. First, it does have some serotonin re-uptake inhibition like the SSRI's. Secondly, it antagonizes certain post-synaptic serotonin receptors, so that more serotonin remains in the synapse where it can exert its antidepressive and anti-anxiety benefits. SSRI's didn't do much for me; my guess (and it's purely a guess) is that serotonin deficiency is not a mahor issue for me, and that unknown, perhaps "down-the-line" effects
of Serzone are what benefit me. I get more of a direct physiological feel from Serzone than I do with the other meds, throughout my body. I feel it surprisingly quickly after taking Serzone, and is a kind of comforting, mildly cooling sensation. (Without Provigil, it might be a very sedating sensation, too!) Also, ss I've mentioned before, I think one of Serzone's main benefits for me is the way it interacts with, potentiates and extends the effects of other meds. That's one reason polypharmacy seems to work well for me. In my case (certainly not for everyone), the interactions and synergies are beneficial rather than detrimental. (I had some concern since Serzone interactions can have hepatic effects -- and it's even caused liver damage by itself in rare cases -- but my recent liver test showed everything to be deep within the normal ranges).Well, if you’ve made it this far in my “essay”, I admire your fortitude. That’s one of the irrational O/C tendencies I have – I feel bad if I leave anything out (Perfectionism? SP-driven approval-seeking?). And I’m a slow writer, to boot. No wonder I don’t have time to get out and do more – social or otherwise! So here’s my resolution: For the next few weeks, any e-mails or forum posts I write will be SHORT!!! (Always easy to say AFTER I finish the tome. Last night I promised myself I wouldn’t get near the internet today. Ha! Better add internet addiction to the list of possible factors. Of course, I go from periods of zero posting to spending all day. I guess you could say I suffer from Bi-Postal disorder.)
Well, dammit, I’m not going to spell-check, even though Dr. Bob wants people to review their posts. So if you saw any mistakes above, you now know why.Rick
> Thanks for the comments Rick!
>
> That was encouraging to hear and my
> first feedback. I hadn't touched the site
> for a couple months and just changed it a bit.
>
> Thanks for your own regimen info.
>
> Can I ask how you rate your improvement on
> your current regimen? (symtom wise anyway);
> it sounds like we both sense a big difference
> between symptom abatement and 'total remission'
>
> I have to admit I'm surprised (but pleased!)
> that the regimen you currently take works so well,
> only because it seems like there wouldn't be much
> overall serotonin increase.
>
> In my case, Serzone and Klonopin both seem to
> give me an anti-serotonin effect, such that either
> one or both together will tend to cause a depression
> in me that I don't have by nature (untreated). Both
> of those meds also tend to reduce serotonin induced
> sexual side effects in my case. Klonopin is
> unquestionably pro-sexual in my case, and Serzone may
> or may not be depending on dose and concurrent
> medication.
>
> Provigil, on the other hand, does reported have
> a pro-serotonin effect and I seem to sense some
> serotonin (and dopamine) effect as well based on
> it's effects.
>
> I did very well on Zoloft+Serzone+Klonopin
> in the past except that laziness and sedation
> were a bit problematic. I think that I probably
> would do very well on Z50+S300+K2-4.5+P100-200.
>
>
>
>
>
>
>
>
>
>
>
> > Thanks for posting!
> >
> > Finally, I find someone who has seen the anti-anxiety potential of the gentle stimulant Provigil! Getting pdocs (let alone GP's) to prescribe it is really tough, because they're unfamiliar with it and convinced it must *cause* anxiety. (I know that some Psycho-Babblers have ordered the related adrafinil from overseas for use in Social Phobia.)
> >
> > I am always interested in hearing how Provigil works in tandem with various AD's, and was especially interested in hearing about a Nardil/Provigil combo. Apparently, it's effective!
> >
> > BTW, I'm now at 1 mg Klonopin (occasionally 1.25 - 1.5); 300 mg Serzone (down again after having been up to 450 for quite awhile), and 100 mg Provigil (with an occasional "rejuvenating" spike to 200 for a day or two). Despite the lower Klonopin dosage, it's still the med I would stick with if I could only choose one. I believe drug interactions make my Klonopin blood levels more comparable to a somewhat higher dose. I've always insisted on branded Klonopin, but due to a recent mixup I ended up getting generic clonazepam a month ago (mf'd by Tiva -- their top-selling med), and it seems equivalent thus far. I don't like the fact that I'm usually left with some Klono-Dust when I split a generic pill, but that doesn't seem to have any theraputic significance.
> >
> > Congratulations on putting together a GREAT website that succinctly but thoroughly -- and without the typical biases -- covers the keypoints of SP and its treatment. Some may quibble with some of the individual treatment recommendations, but there's lots there to help social phobics begin reclaiming their lives. I can really relate to your observations about how it's easier to remedy the "fear of people" than it is to reverse the simple inertia of ingrained, avoidance-generated social habits.
> >
> > The only thing I might personally take issue with is the recommendation of considering caffeine when trying to treat an anxiety disorder. I had always found it hard to believe that caffeine could cause noticeably increased susceptibility to anxiety, but then discovered that it truly can have that effect, at least for me. I'm not saying caffeine reverses the medication benefit, but it does diminish it a bit, so I try to avoid it (or at least moderate my intake) on weekdays. Of course, some social phobic or otherwise anxious inividuals might be immune to caffeine-induced nervousness.
> >
> > BTW, Nardil was the first psychotropic I was ever prescribed, and I quit it because the side effects were intolerable. Back then I had newly-identified high blood pressure (has since gone away, largely due to weight and anxiety reduction), but Nardil took it so far in the other direction that I was spontaneously falling down from dizziness -- in public areas, no less -- and ended up hitting my head more than once. I now realize that I upped my Nardil dosage too quickly despite my pdoc's cautions, and also realize that most of the side effects might have abated with time as you describe (maybe not the sexual dysfunction, though). While I know that the food restrictions are overstated (which is NOT to say "unimportant"!!), and I didn't find them terribly burdensome, the food-fanatic within is glad he doesn't have to adhere to any restrictions at all.
> >
> > Speaking of Nardil and food, despite that med's reputation for causing big weight gain, I actually made my first successful (VERY successful, and sustained) attempt at weight loss while taking the MAOI. Again, YMMV.
> >
> > BTW, I'm glad you wrote this before the "my-deja" e-mail service (and thus the address I had been listing here) is shut-down in a few months. Otherwise, I wouldn't have received Psycho-Babble's automatic e-mail alert about your update to this thread. (I only check back here occasionally, and don't look at the archives.)
> >
> > Rick
Posted by rick_number1001@yahoo.com on August 19, 2001, at 3:31:16
In reply to SP Cocktail - Your Questions+Surprise Enhancer (?) » rick_number1001@yahoo.com, posted by Rick on August 18, 2001, at 16:40:07
Rick:
I want to thank you for your post.
There was a lot there. I hope you saved it in
case you ever want to re-use it! In any case,
I am going to print out your post after this
reply and look at it later. You are the first
person I've communicated with who has a similar
history to mine in many ways. Like youself, I
tend to avoid the Internet but occasionally come
back to it and have at times spent more time than
I intended on it. This still happens to me, in fact
this weekend is a good example.However, I really do appreciate the comprehensive
info. In fact I read your post with much
optomism. And there really should be! I don't
know how bad your SP was untreated but mine was
very severe (according to Liebowitz test anyway)
and if my improvement is 50% or 90% (it's hard
for me to judge too - the symtoms can be treated
well but sometimes I don't feel I have a good handle
on my state of emotional health and "normalcy".
This is a topic I've been discussing the past
couple of times in CBT ("normalcy") - and I'm
getting quite a bit out of it (good things).Anyway - I (probably like you), could write books
on SP. But I'll just curtail this now and thank
you again for the post I'll print out.I wanted to mention also that I posted here
because I was impressed a couple months ago by
some of the threads, they were far more positive
(people getting good results with educated
polypharmacy and experimenation) than posts
I'd seen in the past, mostly several years ago
when I was on newsgroups for a few months.I'm still waiting for someone to tell me how
great Paxil works (still) for their uncomplicated
severe SP.I also wanted to mention that I will see if your
email is on the thread (I'm new here and not
familiar) - but if not I wanted to invite you to
send me a note sometime (I suppose since you've
reviewed my website (THANKS!! one of the very few
...), and my email is there that can work.So I hope to exchange notes (shorter for us both
:) sometime and in the meantime I will keep a
copy of your post saved and printed out for
my own reference.(I'm curious how I'd respond to your regimen -
yours seems to yield excellent results with low
doses of generally very safe and mild medications.)
I am impressed! Congratulations on your continued
discoveries!!!Craig
(rick_number1001 is a pseudoname I invented
for purposes of my website).
> NOTE: THIS IS A LONG POST!
>
> rick_number1001:
>
> Symptom-wise -- which is my priority now that I’m middle-aged and in a stable relationship and career -- I’d say my improvement is about 80-85%, although for the past few weeks it feels more like 90-95% (more on that in a moment). For a slew of reasons, it’s hard to assess “overall” improvement, e.g. including the desire to seek a larger social network and get involved in outside-of-work social situations. There’s a complex mix of rational, irrational (but not psychologically abnormal), and lingering abnormal avoidant/compulsive tendencies that keep me from proactively seeking out social situations, and cause me to turn down invitations. The net result is that most of my fear of social situations has abated, as well as most of the anticipatory anxiety, but I still lean towards a desire to be with myself and those closest to me. Unlike before, though, when I do, say, have to go to a party I don’t worry about it in advance (although I may “resent” it), I’m comfortable when I’m there (a HUGE improvement), and I often end up really enjoying myself instead of dying to make my way to the door. Yet I’m still relieved (and pleased by how I handled it vs. the “old days”) when it’s over, because I can return to my greatest comfort zone.
>
> Sorry about babbling, but that in itself is an indication of how “overall improvement” is hard for me to put a number on (anyone have a Liebowitz scale lying around?). Ironically, this ties in with a much-improved but still lingering SP-related factor: my concern – real or imagined -- that I often have trouble expressing myself.
>
> Regardless, the botom line is that I’m thrilled with the amount of mental burden that has been lifted through my treatment, and the fact that I can really be “me” around other people instead of constantly worrying about what others think and suffering abnormal, troublesome physical and panic-like reactions. (Ironically, perhaps because of my OC tendencies which are still very much at play, when I’m in a previously-fear-inducing situation I sometimes spend an unreasonable amount of time marvelling at how well I’m handling them...kind of an ironic flip-flop of the excessive self-scrutinization that is part of social phobia.)
>
> Believe me, if my current regimen wasn’t working so well, I wouldn’t still be taking the same three meds
> after more than a year. Prior to that, I was on the meds merry-go-round so many of us have dealt with. I’ve experimented with timing and dosages, but that’s it.
>
> That last thought leads me to the even-futher increase in benefit “80% to 90%” that I’ve seen symptomatically in the last few weeks. I hesitated to bring this up for several reasons. One is that I sometimes go through periods where there is a little fluctuation in symptomatic relief, although I’m always far better off than before the combo. But usually these unexplained up-or-down blips last for hours-to-days, not weeks. Now it’s two weeks, and I haven’t experienced even that occasional, minor symptom (e.g., a slight tremor in my voice when I’m put on the spot and someone’s staring in my eyes waiting for me to respond). Another reason I hesitate is because I haven’t been taking the supplement I’m about to mention long enough to assess whether the effect will last. And I’m slightly concerned about safety, since this is not a well-known supplement in the US (it’s widely used in Europe and Japan for various indications). Indeed, I’ve always been skeptical of herbs and “fringe” supplements, and haven’t seen any benefit whatsoever in the past. (“Fringe” is an important word there – I take many supplemets and a multi-vitamin for physical and mental health benefit/protection, including B-Complex, Vit E, One-a-Day Over-50 – even though I’m NOT over 50 – alpha-lipoic acid, and more. It’s likely that in some way these -- and more importantly a few common prescription meds that interact with Serzone -- add to the effectiveness of my SP cocktail, as did weight-loss and caffeine reduction. Now, if I could only get ioff my lazy butt and exercise!)
>
> This over-the-counter supplement is called VINPOCETINE. (I put it in caps in case you or other readers wanted to wade through my excessive babbling and cut to the chase.) It’s a mostly-synthetic derivitive of the Periwinkle plant. I’ve always been skeptical of herbally-based meds (in terms of effectiveness, safety, and product control), but I wanted to see if something might help with the mild memory impairment that is likely due to my meds. (Despite Klonopin’s reputation, some personal experimenting seemed to indicate that the memory impairment was attenuated when I stopped taking Serzone for awhile (but not surprisingly this made my SP treatment somewhat less robust). I also note that I saw no such memory loss until 6 months after adding Serzone and Provigil– after almost a year on a substantially larger dosage of Klonopin. As an aside, I saw one post where someone complained of memory deficit from Provigil , despite its purported memory-enhancing benefits...hmm).
>
> Anyway, I *may* be seeing a litte memory benefit with Vinpocetine, but I’m not so sure. What I *have* noticed – even though this isn’t generally mentioned for this supplement – is added “fortification” of my already-strong Social Phobia cocktail. It seems to iron out the chinks that remain, add a smoothness and consistency. The purported cognitive benefit of Vinpocetine was originally (and sometimes still) thought to come from increased blood circulation and glucose utilization localized to the brain (vs. Ginkgo, which has a similar effect but throughout the whole body). Now the memory impact is thought to likely derive from neuronal protection.
>
> What I’m seeing from Vinpocetine (Nature Made brand) is a simultaneously stimulating but calming effect, kind of like something that takes up where Provigil leaves off. I’m getting way out of my league here, but the American Journal of Psychiatry recentlt had an article detaining reduced blood flow in SP subjects vs. normal subjects when forced into a public speaking situation. SP’s started out with lower flow in many areas of the brain, and during the challenge SP cerebral blood flow actually dropped some, while there was a sahrp increase among normal subjects. While cause-vs.-effect isn’t clear, and I hardly understand all the nuances and might be drawing some overly-simplistic or plain-wrong conclusions, but is it possible Vinpocetine’s increased cerebral blood flow is compensating for an SP-induced decline that may accompany my “chink in the armor” moments? I also note that the med (it really *is* more of a drug than an herb) has been used in epilepsy, and there seems to be a strong overlap between meds that can be useful in epilepsy and social anxiety, e.g. Klonopin, Neurontin.
>
> While there could be a placebo effect here, the mild-stimulation effect feels very real. And Vinpocetine is clearly doing *something* because I’ve had a 10-15 point drop in my blood glucose across the board. (I’m not diabetic – at least not “officially” -- but had one high reading during a test a few years ago. That’s when I started my diet and anxiety treatment, and I still monitor every few days. I’ve been normal to high-normal all along, but since staring Vinpocetine I’ve been in the low-normal range, which is the best place to be in most cases.) And maybe this is just by chance again, but for the last few weeks I’ve felt a lot more sexually charged, if you will (there was no dysfuntion before; I’m speaking of enhancement).
>
> Perhaps most importantly, I’ve cut my Serzone back to 300 mg again, Klonopin to 1 mg, and haven’t felt the occasional need for a temporary boost in Provigil dose. AND...I’m now taking all of the psychotrpoics in the morning only (even though Serzone has a short half-life), while taking Vinpocetine three times a day. The ony exception was an extra .25 mg Klonopin before a party. It’s too early to judge, but right now I’m sticking with it. And if memory benefits DO kick in, that would be great – since that’s why I tried Vinpocetine in the first place! I seem to have a history of unexpected benefits from meds, especially Klonopin and Provigil. In fact, you are one of the few people besides myself that I’ve seen report sexual *enhancement* from Klonopin. Despite hundreds of references to Vinpocetine on Medline, I do wish I knew more about its long-term safety, and any “bad” interactions with other meds or supplements. In particular, there is “some evidence” that it has anticoagulant properties, which is probably good in general but I’d really like to keep taking my daily preventative baby aspirin yet I’m afraid of the risks associated with excessive blood-thinning.
>
> But with all my gabbing about Vinpocetine, I don’t want to lose sight of the more important point. Namely, that after more than a year I’m still thrilled with the combo of Klonopin, Provigil and Serzone for non-depressive Social Phobia. Not the slightest indication of poop-out.
>
> I’ve been warned that, “you WILL experience depression from Klonopin at some point.” And there have been occasional days that seemed pretty dark mentally (interestingly, this happened most recently when I had to go about five days without Provigil), but they pass quickly and I don’t think they really come close to clinical depression (if protracted, I guess they might qualify as dysthmia). In fact, largely due some lucky breaks in life, my Social Phobia has never led to clinical depression. There may have been one period where I could have had undiagnosed depression, during a period of deep grief exacerbated by a slew of factors surrounding my mother’s brain cancer that made it maximally shocking and difficult to deal with.
>
> As for serotonergic effects, the studies I've seen generally conclude that Klonopin causes anything from a mild decrease to a mild increase in serotinin availability. Klonopin apparently DOES cause an inhibitory pre-synaptic seorotin release, but this effect is balance by other, pro-serotnergic effects. As for Serzone, it IS a serotenergic (and somewhhat adrenergic) medication. First, it does have some serotonin re-uptake inhibition like the SSRI's. Secondly, it antagonizes certain post-synaptic serotonin receptors, so that more serotonin remains in the synapse where it can exert its antidepressive and anti-anxiety benefits. SSRI's didn't do much for me; my guess (and it's purely a guess) is that serotonin deficiency is not a mahor issue for me, and that unknown, perhaps "down-the-line" effects
> of Serzone are what benefit me. I get more of a direct physiological feel from Serzone than I do with the other meds, throughout my body. I feel it surprisingly quickly after taking Serzone, and is a kind of comforting, mildly cooling sensation. (Without Provigil, it might be a very sedating sensation, too!) Also, ss I've mentioned before, I think one of Serzone's main benefits for me is the way it interacts with, potentiates and extends the effects of other meds. That's one reason polypharmacy seems to work well for me. In my case (certainly not for everyone), the interactions and synergies are beneficial rather than detrimental. (I had some concern since Serzone interactions can have hepatic effects -- and it's even caused liver damage by itself in rare cases -- but my recent liver test showed everything to be deep within the normal ranges).
>
> Well, if you’ve made it this far in my “essay”, I admire your fortitude. That’s one of the irrational O/C tendencies I have – I feel bad if I leave anything out (Perfectionism? SP-driven approval-seeking?). And I’m a slow writer, to boot. No wonder I don’t have time to get out and do more – social or otherwise! So here’s my resolution: For the next few weeks, any e-mails or forum posts I write will be SHORT!!! (Always easy to say AFTER I finish the tome. Last night I promised myself I wouldn’t get near the internet today. Ha! Better add internet addiction to the list of possible factors. Of course, I go from periods of zero posting to spending all day. I guess you could say I suffer from Bi-Postal disorder.)
> Well, dammit, I’m not going to spell-check, even though Dr. Bob wants people to review their posts. So if you saw any mistakes above, you now know why.
>
> Rick
>
>
> > Thanks for the comments Rick!
> >
> > That was encouraging to hear and my
> > first feedback. I hadn't touched the site
> > for a couple months and just changed it a bit.
> >
> > Thanks for your own regimen info.
> >
> > Can I ask how you rate your improvement on
> > your current regimen? (symtom wise anyway);
> > it sounds like we both sense a big difference
> > between symptom abatement and 'total remission'
> >
> > I have to admit I'm surprised (but pleased!)
> > that the regimen you currently take works so well,
> > only because it seems like there wouldn't be much
> > overall serotonin increase.
> >
> > In my case, Serzone and Klonopin both seem to
> > give me an anti-serotonin effect, such that either
> > one or both together will tend to cause a depression
> > in me that I don't have by nature (untreated). Both
> > of those meds also tend to reduce serotonin induced
> > sexual side effects in my case. Klonopin is
> > unquestionably pro-sexual in my case, and Serzone may
> > or may not be depending on dose and concurrent
> > medication.
> >
> > Provigil, on the other hand, does reported have
> > a pro-serotonin effect and I seem to sense some
> > serotonin (and dopamine) effect as well based on
> > it's effects.
> >
> > I did very well on Zoloft+Serzone+Klonopin
> > in the past except that laziness and sedation
> > were a bit problematic. I think that I probably
> > would do very well on Z50+S300+K2-4.5+P100-200.
> >
> >
> >
> >
> >
> >
> >
> >
> >
> >
> >
> > > Thanks for posting!
> > >
> > > Finally, I find someone who has seen the anti-anxiety potential of the gentle stimulant Provigil! Getting pdocs (let alone GP's) to prescribe it is really tough, because they're unfamiliar with it and convinced it must *cause* anxiety. (I know that some Psycho-Babblers have ordered the related adrafinil from overseas for use in Social Phobia.)
> > >
> > > I am always interested in hearing how Provigil works in tandem with various AD's, and was especially interested in hearing about a Nardil/Provigil combo. Apparently, it's effective!
> > >
> > > BTW, I'm now at 1 mg Klonopin (occasionally 1.25 - 1.5); 300 mg Serzone (down again after having been up to 450 for quite awhile), and 100 mg Provigil (with an occasional "rejuvenating" spike to 200 for a day or two). Despite the lower Klonopin dosage, it's still the med I would stick with if I could only choose one. I believe drug interactions make my Klonopin blood levels more comparable to a somewhat higher dose. I've always insisted on branded Klonopin, but due to a recent mixup I ended up getting generic clonazepam a month ago (mf'd by Tiva -- their top-selling med), and it seems equivalent thus far. I don't like the fact that I'm usually left with some Klono-Dust when I split a generic pill, but that doesn't seem to have any theraputic significance.
> > >
> > > Congratulations on putting together a GREAT website that succinctly but thoroughly -- and without the typical biases -- covers the keypoints of SP and its treatment. Some may quibble with some of the individual treatment recommendations, but there's lots there to help social phobics begin reclaiming their lives. I can really relate to your observations about how it's easier to remedy the "fear of people" than it is to reverse the simple inertia of ingrained, avoidance-generated social habits.
> > >
> > > The only thing I might personally take issue with is the recommendation of considering caffeine when trying to treat an anxiety disorder. I had always found it hard to believe that caffeine could cause noticeably increased susceptibility to anxiety, but then discovered that it truly can have that effect, at least for me. I'm not saying caffeine reverses the medication benefit, but it does diminish it a bit, so I try to avoid it (or at least moderate my intake) on weekdays. Of course, some social phobic or otherwise anxious inividuals might be immune to caffeine-induced nervousness.
> > >
> > > BTW, Nardil was the first psychotropic I was ever prescribed, and I quit it because the side effects were intolerable. Back then I had newly-identified high blood pressure (has since gone away, largely due to weight and anxiety reduction), but Nardil took it so far in the other direction that I was spontaneously falling down from dizziness -- in public areas, no less -- and ended up hitting my head more than once. I now realize that I upped my Nardil dosage too quickly despite my pdoc's cautions, and also realize that most of the side effects might have abated with time as you describe (maybe not the sexual dysfunction, though). While I know that the food restrictions are overstated (which is NOT to say "unimportant"!!), and I didn't find them terribly burdensome, the food-fanatic within is glad he doesn't have to adhere to any restrictions at all.
> > >
> > > Speaking of Nardil and food, despite that med's reputation for causing big weight gain, I actually made my first successful (VERY successful, and sustained) attempt at weight loss while taking the MAOI. Again, YMMV.
> > >
> > > BTW, I'm glad you wrote this before the "my-deja" e-mail service (and thus the address I had been listing here) is shut-down in a few months. Otherwise, I wouldn't have received Psycho-Babble's automatic e-mail alert about your update to this thread. (I only check back here occasionally, and don't look at the archives.)
> > >
> > > Rick
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