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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by Dave001 on July 15, 2005, at 21:29:21
There is some evidence that certain serotonin uptake inhibitors are less
likely than others to adversely affect cognition. Sertraline (Zoloft in
the U.S.) in particular has compared favorably on this measure in
several human clinical trials. The prevalent hypothesis is that
sertraline's mild inhibitory effect on dopamine uptake helps counteract
some of the common SSRI induced side-effects that are thought to be
mediated by dopamine.However, there is still the question of whether all SSRIs invariably
lead to suboptimal changes of dopamine-dependent parameters of
functioning, even if aggressive dopaminergic therapies are added in an
attempt to reverse these untoward deficits. Perhaps a drug with dual
agonist/antagonist action at the serotonin receptor might be an ideal
strategy for those who benefit from SSRIs but find the side-effects
intolerable.Who has tried sertraline in addition to at least one other SSRI? I'm
interested to see how well the results from the studies mirror your
experiences? Do _you_ feel that sertraline had a lesser degree of
"dopamine-dependent" side-effects (see references and abstracts) than
other SSRIs? Among the SSRIs, which have you tried in addition to
sertraline, and how did they compare?Dave
References:
Damsa, C., A. Bumb, et al. (2004). "'Dopamine-dependent' side effects of
selective serotonin reuptake inhibitors: a clinical review." Journal of
Clinical Psychiatry 65(8): 1064-8.Furlan, P. M., M. J. Kallan, et al. (2001). "Cognitive and Psychomotor
Effects of Paroxetine and Sertraline on Healthy Elderly Volunteers."
American Journal of Geriatric Psychiatry 9(4): 429-438.Riedel, W. J., K. Eikmans, et al. (2005). "Specific serotonergic
reuptake inhibition impairs vigilance performance acutely and after
subchronic treatment." Journal of Psychopharmacology 19(1): 12-20.Schmitt, J. A., J. G. Ramaekers, et al. (2002). "Additional dopamine
reuptake inhibition attenuates vigilance impairment induced by serotonin
reuptake inhibition in man." Journal of Psychopharmacology 16(3): 207-14.Barnhart, W. J., E. H. Makela, et al. (2004). "SSRI-induced apathy
syndrome: a clinical review." Journal of Psychiatric Practice 10(3): 196-9.Avila, A., X. Cardona, et al. (2003). "Does nefazodone improve both
depression and Parkinson disease? A pilot randomized trial." Journal of
Clinical Psychopharmacology 23(5): 509-13.Marek, G. J., L. L. Carpenter, et al. (2003). "Synergistic action of
5-HT2A antagonists and selective serotonin reuptake inhibitors in
neuropsychiatric disorders." Neuropsychopharmacology 28(2): 402-12.
Citations from above with abstracts (I kept the abstracts separate for
easier navigation):Riedel, W. J., K. Eikmans, et al. (2005). "Specific serotonergic
reuptake inhibition impairs vigilance performance acutely and after
subchronic treatment." Journal of Psychopharmacology 19(1): 12-20.Subchronic treatment with the selective serotonergic reuptake inhibitors
(SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were
previously shown to specifically impair vigilance performance. The
current study was designed to compare the vigilance effects of
subchronic treatment with the SSRIs sertraline and citalopram in healthy
volunteers, according to a placebo-controlled, double-blind, three-way
cross-over design. Twenty-four healthy subjects, aged 30-50 years, of
whom 21 completed the study, underwent three treatment periods of 2
weeks in which they received sertraline (50 mg on days 1-8, 100 mg on
days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and
placebo. Treatment periods were separated by 14 days washout periods.
Vigilance performance was assessed through a 45-min Mackworth Clock Test
at days 1, 8 and 15 of each treatment period. It was found that
citalopram impaired vigilance performance acutely after the first 20 mg
dose and subchronically after 40 mg daily doses. By contrast, no
vigilance impairment was found during sertraline treatment. Sertraline
is the only SSRI studied so far with no detrimental effects on
vigilance. This may be due to the affinity of sertraline for the
dopamine reuptake site. Because citalopram is the most specific SSRI
showing this effect, it is concluded that the SSRI-induced decrement of
vigilance performance is specifically associated with serotonergic
reuptake inhibition.
Damsa, C., A. Bumb, et al. (2004). "'Dopamine-dependent' side effects of
selective serotonin reuptake inhibitors: a clinical review." Journal of
Clinical Psychiatry 65(8): 1064-8.OBJECTIVE: Neurophysiologic findings indicate an inhibition of
dopaminergic neurotransmission by selective serotonin reuptake
inhibitors (SSRIs). This article highlights the relationships between
changes in dopaminergic neurotrans-mission induced by SSRIs and the
occurrence of certain side effects such as hyperprolactinemia,
extrapyramidal symptoms, sexual and cognitive dysfunction, galactorrhea,
mammary hypertrophy, and, more rarely, gynecomastia. DATA SOURCES AND
SELECTION: A systematic search of the literature in English, French, and
German from 1980 to 2004 was performed in MEDLINE, EMBASE, and the
Cochrane Library using the keywords SSRI, dopamine, serotonin, side
effects, antidepressants, citalopram, escitalopram, sertraline,
paroxetine, fluoxetine, fluvoxamine, and nefazodone. References cited in
all trials were searched iteratively to identify missing studies. All
studies concerning inhibition of dopaminergic neurotransmission by SSRIs
and SSRI-related side effects were considered. We retained 62
significant articles debating the subject. DATA EXTRACTION AND
SYNTHESIS: We critically reviewed the studies, depending on the
methodologies (case reports, clinical reports, randomized studies), and
assessed the pertinence of "dopamine-dependent" SSRI-related side
effects. The analytic review of these articles suggests that some
specific SSRI-related side effects be classified as dopamine-dependent.
CONCLUSIONS: At a clinical level, it could be useful to underline
dopamine-dependent characteristics of some SSRI-related side effects.
This approach would allow clinicians the opportunity to search other
dopamine-dependent side effects systematically. At a pharmacologic
level, this approach could stimulate the development of molecules with a
"corrective" function on dopamine-dependent side effects of SSRIs by
facilitating dopaminergic neurotransmission.
Schmitt, J. A., J. G. Ramaekers, et al. (2002). "Additional dopamine
reuptake inhibition attenuates vigilance impairment induced by serotonin
reuptake inhibition in man." Journal of Psychopharmacology 16(3): 207-14.There is evidence for a specific impairment of human vigilance following
enhancement of serotonergic activity by antidepressant drugs. In the
present study, we investigated the putative role of
serotonergic-dopaminergic interactions in diminished vigilance by
comparing the attentional effects of sertraline, a selective serotonin
reuptake inhibitor (SSRI) with additional mild dopamine stimulating
effects, with those of paroxetine, a SSRI without dopamine activity,
using a placebo-controlled, double-blind, three-way cross-over design.
Twenty-one (of 24) healthy middle-aged subjects completed the three
treatment periods of 2 weeks in which sertraline (50 mg, days 1-7; 100
mg, days 8-14), paroxetine (20 mg, days 1-7; 40 mg, days 8-14) and
placebo were administered. Vigilance (Mackworth Clock Test), selective
(Stroop, Dichotic Listening) and divided attention (Dichotic Listening)
were assessed at baseline and on days 7 and 14 of each treatment period.
Selective and divided attention were unaffected by SSRI treatment.
Subchronic administration of paroxetine impaired vigilance performance
at each investigated dose. Sertraline did not produce a significant
decline in vigilance performance, presumably due to its concomitant
effects on dopamine activity, counteracting the negative effects of
serotonin on dopamine neurotransmission. It is concluded that a
serotonergically mediated reduction of dopamine activity plays an
important role in the reduction of human vigilance following SSRI
administration.
Furlan, P. M., M. J. Kallan, et al. (2001). "Cognitive and Psychomotor
Effects of Paroxetine and Sertraline on Healthy Elderly Volunteers."
American Journal of Geriatric Psychiatry 9(4): 429-438.The authors evaluated the cognitive and psychomotor effects of serotonin
reuptake inhibitors in healthy elderly volunteers. Paroxetine,
sertraline, and placebo were compared for 3 weeks of testing in a
double-blind study with behavioral testing at baseline and at the end of
each week. MANOVA models demonstrated no between-group differences;
however, mixed-model random regression analyses revealed that Day 14
plasma paroxetine levels correlated negatively with delayed verbal
recall and paired-associate learning scores. In contrast, plasma
sertraline levels correlated positively with Day 7 immediate verbal
recall, Day 14 tapping, and Day 21 delayed verbal recall scores, and
negatively with divided-attention task scores on Day 21. Plasma
paroxetine levels were associated with mild behavioral impairment at Day
14, with no other significant adverse effects. Plasma sertraline levels
were associated with mild and transient behavioral changes, as well as
early termination in several subjects.
Barnhart, W. J., E. H. Makela, et al. (2004). "SSRI-induced apathy
syndrome: a clinical review." Journal of Psychiatric Practice 10(3): 196-9.The authors review the literature pertaining to selective serotonin
reuptake inhibitor (SSRI)-induced apathy syndrome. A literature search
of Medline and International Pharmaceutical Abstracts from 1970 to the
present was performed for relevant articles. Twelve relevant case
reports and one open-label treatment trial were identified. An
amotivational, or apathy, syndrome has been reported in a number of
patients receiving SSRI treatment over the last decade. This adverse
effect has been noted to be dose-dependent and reversible, but is often
unrecognized. This phenomenon has caused significant negative
consequences for adults as well as social and academic difficulties in
adolescents.
Avila, A., X. Cardona, et al. (2003). "Does nefazodone improve both
depression and Parkinson disease? A pilot randomized trial." Journal of
Clinical Psychopharmacology 23(5): 509-13.Some of the selective serotonin reuptake inhibitors (SSRI)-induced motor
side effects are mediated by stimulating 5-HT2 receptors in the basal
ganglia, probably because serotonin inhibits the subsequent neuronal
dopamine release. We hypothesized that nefazodone, a serotonin 2
antagonist/reuptake inhibitor (SARI) that selectively blocks 5-HT2
receptors, could disrupt the aforementioned inhibitory pathway.
Therefore, increased dopamine levels in the postsynaptic milieu and an
improvement in the motor symptoms in depressed patients with Parkinson
disease (PD) should be observed. This study was designed to determine
whether nefazodone has a dual activity as an antidepressant and as an
agent capable of reducing the extrapyramidal symptoms in depressed
parkinsonian patients. Depressed patients with PD were randomly assigned
to 2 therapeutic groups: nefazodone or fluoxetine. Patients were
evaluated by a psychiatrist and were blindly assessed by a neurologist
with an array of scales. Patients on nefazodone (n = 9) showed a
significant improvement over time in the total Unified Parkinson Disease
Rating Scale score (UPDRS) (part II + part III) (P = 0.004) and in the
UPDRS subscore part III (P = 0.003). None of these scores changed over
time in the fluoxetine group (n = 7). Both, nefazodone and fluoxetine
were equally effective as antidepressants: Beck Depression Inventory
scores significantly improved (P < 0.001), with no significant
differences between treatment groups (P = 0.97). If our results can be
confirmed in a larger clinical trial, nefazodone ought to be considered
over fluoxetine given its secondary beneficial effects regarding the
reduction of extrapyramidal symptoms in depressed PD patients.
Marek, G. J., L. L. Carpenter, et al. (2003). "Synergistic action of
5-HT2A antagonists and selective serotonin reuptake inhibitors in
neuropsychiatric disorders." Neuropsychopharmacology 28(2): 402-12.Recently, the addition of drugs with prominent 5-HT(2) receptor
antagonist properties (risperidone, olanzapine, mirtazapine, and
mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been
shown to enhance therapeutic responses in patients with major depression
and treatment-refractory obsessive-compulsive disorder (OCD). These
5-HT(2) antagonists may also be effective in ameliorating some symptoms
associated with autism and other pervasive developmental disorders
(PDDs). At the doses used, these drugs would be expected to saturate
5-HT(2A) receptors. These findings suggest that the simultaneous
blockade of 5-HT(2A) receptors and activation of an unknown
constellation of other 5-HT receptors indirectly as a result of 5-HT
uptake inhibition might have greater therapeutic efficacy than either
action alone. Animal studies have suggested that activation of 5-HT(1A)
and 5-HT(2C) receptors may counteract the effects of activating 5-HT(2A)
receptors. Additional 5-HT receptors, such as the 5-HT(1B/1D/5/7)
receptors, may similarly counteract the effects of 5-HT(2A) receptor
activation. These clinical and preclinical observations suggest that the
combination of highly selective 5-HT(2A) antagonists and SSRIs, as well
as strategies to combine high-potency 5-HT(2A) receptor and 5-HT
transporter blockade in a single compound, offer the potential for
therapeutic advances in a number of neuropsychiatric disorders.
Kugaya, A., N. M. Seneca, et al. (2003). "Changes in human in vivo
serotonin and dopamine transporter availabilities during chronic
antidepressant administration." Neuropsychopharmacology 28(2): 413-20.Few studies have demonstrated in vivo alterations of human serotonin and
dopamine transporters (SERTS and DATS) during antidepressant treatment.
The current study measured these transporter availabilities with
[(123)I]beta-CIT single photon emission computed tomography (SPECT)
during administration of selective serotonin reuptake inhibitors (SSRIs)
or a non-SSRI, bupropion. A total of 17 healthy human subjects were
randomly assigned to two different treatment protocols: (1). citalopram
(40 mg/day) followed by augmentation with bupropion (100 mg/day) or (2).
bupropion (100-200 mg/day) for 16 days. Citalopram significantly
inhibited [(123)I]beta-CIT binding to SERT in brainstem (51.4%) and
diencephalon (39.4%) after 8 days of administration, which was similarly
observed after 16 days. In contrast, citalopram significantly increased
striatal DAT binding by 15-17% after 8 and 16 days of administration.
Bupropion and its augmentation to citalopram did not have a significant
effect on DAT or SERT. In 10 depressed patients who were treated with
paroxetine (20 mg/day), a similar increase in DAT and inhibition of SERT
were observed during 6 weeks treatment. The results demonstrated the
inhibition of SERT by SSRI in human in vivo during the chronic treatment
and, unexpectedly, an elevation of DAT. This apparent SSRI-induced
modulation of the dopamine system may be associated with the side
effects of these agents, including sexual dysfunction.
Posted by TerraJo on July 15, 2005, at 22:17:48
In reply to SSRIs and cognition: what's your experience?, posted by Dave001 on July 15, 2005, at 21:29:21
I don't know what my conclusion is based on the questions you posed, but here's my experience.
prozac- i tried it. honestly can't remember (no pun intended)
paxil- won't try because of the weight gain side effect.
zoloft- made me suicidal.
luvox- didn't try. not applicable to my situation.
lexapro (celexa)- made me lethargic and tired
serzone- loved, but could not get high enough dose w/o brain zapping/lightning flashes
effexor- made me crazy. don't know how else to describe it. but that's how i felt. i hated it.
wellbutrin- currently on and love it.
Posted by linkadge on July 16, 2005, at 0:24:50
In reply to Re: SSRIs and cognition: what's your experience?, posted by TerraJo on July 15, 2005, at 22:17:48
I have had cognative problems on all SSRI's.
The remeron / celexa combiation did not affect my cognition as adversly.
Linkadge
Posted by JayDee on July 16, 2005, at 1:05:29
In reply to Re: SSRIs and cognition: what's your experience?, posted by linkadge on July 16, 2005, at 0:24:50
getting slower and slower on Prozac. im cutting myself down to 30mg, dumping out half of one of my 20mg pills. my first day, today, a little angry, a little more energy.
I dont see switching to zoloft helping, its DRI properties are quite weak and if I want DRI I have amphetamines for that.
has anyone compared MAOI and SSRI COGNITIVE side effects?
im well aware of the other side effects of MAOI's.
Posted by Declan on July 16, 2005, at 2:53:35
In reply to Re: SSRIs and cognition: what's your experience?, posted by JayDee on July 16, 2005, at 1:05:29
Hopefully I dunno, the cognitive effects of MAOIs are positive. But someone was talking about how Nardil made her feel really weird so its individual and dose related I guess.
Declan
Posted by linkadge on July 16, 2005, at 3:19:17
In reply to Re: MAOIs and cognition, posted by Declan on July 16, 2005, at 2:53:35
Parnate had no cognative effects for me, and even improved my attention problems which did not resolve even after SSRI's were discontinued.
Linkadge
Posted by JayDee on July 16, 2005, at 10:25:18
In reply to Re: MAOIs and cognition, posted by linkadge on July 16, 2005, at 3:19:17
> Parnate had no cognative effects for me, and even improved my attention problems which did not resolve even after SSRI's were discontinued.
>
> Linkadge
why are you no longer on parnate, Linkadge?
Posted by linkadge on July 16, 2005, at 15:04:10
In reply to Re: MAOIs and cognition » linkadge, posted by JayDee on July 16, 2005, at 10:25:18
Just had some weird experiences. It was really intense, and I had really bad tachycardia.
Linkadge
Posted by Dave001 on July 18, 2005, at 21:35:07
In reply to Re: SSRIs and cognition: what's your experience?, posted by JayDee on July 16, 2005, at 1:05:29
> I dont see switching to zoloft helping, its DRI properties are quite
> weak and if I want DRI I have amphetamines for that.Did you read the results of the studies from the abstracts that I posted?
Posted by Cairo on July 24, 2005, at 9:24:16
In reply to Re: SSRIs and cognition: what's your experience?, posted by Dave001 on July 18, 2005, at 21:35:07
Lexapro caused major cognitive problems in my daughter. Switching to Zoloft helped immensely with improved short term memory, less apathy, more desire to socialize. I believe Zoloft's higher affinity for the dopamine receptor is the reason:
http://www.preskorn.com/books/ssri_s3.html#tab3-3
http://www.preskorn.com/columns/0005.html
Cairo
>
> > I dont see switching to zoloft helping, its DRI properties are quite
> > weak and if I want DRI I have amphetamines for that.
>
> Did you read the results of the studies from the abstracts that I posted?
>
>
Posted by Pervoneurotica on November 23, 2005, at 18:24:46
In reply to SSRIs and cognition: what's your experience?, posted by Dave001 on July 15, 2005, at 21:29:21
Hello, I'm a new member - 26 year old female, diagnosed with depression.
I was using Sertraline (Zoloft) intermittently for about 3 years (during the last year I was on it continuously). I kept having to up the dosage, eventually reaching 200mg. I never noticed any side effects, except a very occasional inability to reach orgasm and perhaps anger attacks. If I abruptly discontinued Zoloft, withdrawal symptoms of nausea and confusion were very prominent.
So, I was on the highest dose of 200mg for about 1 year and when it wasn't doing much, I weaned myself off. A little over a month later I noticed symptoms, which I never attributed to the med b/c I was actually not using it anymore.
These symptoms include:
1)reduced sexual desire (VERY abnormal for me -- I have been hypersexual my entire life)
2)reduced frequency of fantasy, sexual thoughts, & masturbation (once again, this would be a very dramatic change in a person such as myself).
3)vaginal dryness (prominent and NEVER a problem before)The vaginal dryness became a big issue; I thought its cause was a hormonal problem (i.e. hyperprolactinemia from a pituitary microadenoma!). In agreement with my 'hormonal' theory, I also noticed I was experiencing less acne.
I ignored the problem and started using KY. I also sampled Venlafaxine (Effexor)for a few months, but it didn't seem to do much, so I switched to Escitalopram (Lexapro), 20mg - the med I am currently taking.
Note: my initial hormonal symptoms never went away. Added to them now is intense nighttime insomnia. Still, I'd choose these S/E's over constant suicide ideation & misery.
According to PubMed, hyperprolactinemia (a dopamine-dependent side effect) is sometimes associated with SSRIs. Should I still get scanned for a brain tumor??
Posted by gibber on November 27, 2005, at 0:06:51
In reply to SSRIs and cognition: what's your experience?, posted by Dave001 on July 15, 2005, at 21:29:21
I have been off prozac and stattera for almost 4 weeks now. The first two week were better than any time while I was on the drugs. The sexual SEs were bad of course but it has not been since being off them that I realized how numb and apathetic they made me. I have been reading more and understand and thinking critically of the material since stopping the drugs. In general I am analysing things more and generally more critical of movies, books and people. Essentially these SSRIs have been all the same for me...they make me numb. I have tried Lexapro and effexor too. The good times these last few weeks have been better, but the bad times have been worse than usual. If I'm feeling bad my cognition goes down the tube. It leaves me wondering whethers it better to be numb or to feel OK and more alive but also experience more very deep depressions. I don't think numbness is a goal of meds and therefore I haven't found the right med yet. ...trying the MAOIs next
Posted by ed_uk on November 27, 2005, at 11:09:56
In reply to Re: SSRIs and cognition: what's your experience?, posted by gibber on November 27, 2005, at 0:06:51
Hi!
Regarding ADs, the more 'stimulating' non-serotonergic tricyclics such as desipramine rarely make people feel numb. Nortriptyline is another option.
Ed
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