Posted by Quintal on August 23, 2007, at 10:48:46
In reply to Re: Parnate/Dexedrine/500 sleeping meds, please he, posted by dopaminerequiem on August 23, 2007, at 9:46:40
>I can't take opiates because I am a former heroin addict. Pretty severely so.
Ahh, I think understand why :o) Well, the interesting thing is that when I ran out of codeine a few months ago I discovered quite by accident that Mirapex suppressed my withdrawal symptoms. It reminded me of the 'nodding phase' of opiate intoxication. This inspired me to do a bit of research, and this is what I found:
http://www.dr-bob.org/babble/20070730/msgs/773860.htmlI don't think Requip or Mirapex would be an effective monotherapy for insomnia. Although sleep attacks are a common side effect at high doses, dopamine agonists are not sedatives as such and they won't reliably put you to sleep on demand as conventional hypnotics (can) do. I think Requip and Mirapex are the only dopamine agonists considered suitable for everyday use in non-Parkinson's patients, because the ergot-derived ones have been associated with fibrotic reactions and cardiac valve defects.
There seems to be more research on efficacy of pramipexole (Mirapex) in mood and anxiety disorders at present, but ropinirole too has shown robust effects in clinical trials in those conditions, and antidepressant-induced sexual dysfunction.
__________________________________________________1: CNS Spectr. 2006 Mar;11(3):172-5.Links
Pramipexole: augmentation in the treatment of depressive symptoms.
Gupta S, Vincent JL, Frank B.Department of Psychiatry, University of Buffalo School of Medicine, USA. sgupta1@adelphia.net
We describe a retrospective case series of three patients, two with bipolar depression and one with unipolar depression. Pramipexole is a Food and Drug Administration-approved antiparkinsonian agent, which, when used to augment antidepressants, would be considered an off-label use and should be discussed with the patient. These patients had robust responses to pramipexole augmentation of their treatment regimen. All three patients had been taking an atypical antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating Scale for Depression.
PMID: 16575373 [PubMed - indexed for MEDLINE]
--------------------------------------------------2: Biol Psychiatry. 2004 Jul 1;56(1):54-60.Click here to read Links
Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK.Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA.
BACKGROUND: The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression. METHODS: In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale. RESULTS: All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p =.02). One subject on pramipexole and two on placebo developed hypomanic symptoms. CONCLUSIONS: The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.
PMID: 15219473 [PubMed - indexed for MEDLINE
--------------------------------------------------3: Bipolar Disord. 2002 Oct;4(5):307-14.Click here to read Links
Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy. paolo.cassano@psico.med.unipi.it
OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
PMID: 12479663 [PubMed - indexed for MEDLINE]
--------------------------------------------------4: Am J Psychiatry. 2004 Mar;161(3):564-6.Click here to read Links
Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.
Goldberg JF, Burdick KE, Endick CJ.Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA. jgoldber1@lij.edu
OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.
PMID: 14992985 [PubMed - indexed for MEDLINE]
--------------------------------------------------5: Depress Anxiety. 2004;20(3):131-8.Click here to read Links
Pramipexole in treatment-resistant depression: an extended follow-up.
Cassano P, Lattanzi L, Soldani F, Navari S, Battistini G, Gemignani A, Cassano GB.Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. pcassano@partners.org
We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score= <2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression. (c) 2004 Wiley-Liss, Inc.
PMID: 15549689 [PubMed - indexed for MEDLINE]
--------------------------------------------------6: Depress Anxiety. 2000;11(2):58-65.Click here to read Links
Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.
Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL.Pharmacia & Upjohn, Inc., Global Clinical Research, Bridgewater, NJ 08807-0995, USA.
Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day.
PMID: 10812530 [PubMed - indexed for MEDLINE]
--------------------------------------------------7: Pharmacopsychiatry. 2001 Jul;34(4):137-41.Links
Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series.
Perugi G, Toni C, Ruffolo G, Frare F, Akiskal H.Department of Psychiatry, University of Pisa, Italy. gperugi@psico.med.unipi.it
OBJECTIVE: Previous studies and case observations have suggested that dopamine agonists (DAAs) such as pramipexole (PPX) and ropinirole (RPN) might be effective for major depression, but their adjunctive use in treatment-resistant bipolar II depression has not yet been specifically addressed. METHOD: A chart review was conducted on 18 patients with a DSM-III-R bipolar NOS (Bipolar II) major depressive episode who were admitted to the day-hospital of the Department of Psychiatry at the University of Pisa. DAAs were added to ongoing treatments with conventional antidepressants and mood stabilizers to which patients had no responded after a period of at least 8 weeks. Clinical state and adverse effects were assessed at each visit. Final improvement in CGI scores of 1 or 2 were considered as responders. RESULTS: Mean DAA trial duration was 17.6 (sd = 7.8, range 4-34) weeks, with a mean final dose of 1.23+/-0.32 mg/day (range, 0.75-1.50mg/day) for PPX, and 2.97+/-0.99mg/day (range, 1.50-5.00mg/day) for RPN. DAAs were well tolerated and did not show any negative interaction with concomitant psychotropic medications. Only one patient became worse (final CGI = 5), and had to interrupt PPX due to nausea, increased agitation and irritability. Eight patients (44.4%) were considered responders (4 with PPX and 4 with RPN): 5 showed marked improvement (CGI = 1), and 3 showed moderate improvement (CGI = 2); another 5 (27.8%) manifested a transient response not sustained up to the end. The initial and final scores of CGI severity scale for all patients (responders and non-responders combined) were, respectively, 5.33+/-0.7 and 3.94+/-1.3 (mean +/- S.D). The mean change according to the CCI severity scale was statistically significant (t=4.74. p < 0.0002). CONCLUSION: From the results, PPX and RPN appear to be well tolerated and potentially useful in the adjunctive treatment of drug-resistant bipolar II depression.
PMID: 11518474 [PubMed - indexed for MEDLINE]
--------------------------------------------------8: Nervenarzt. 2007 Jan;78(1):31-8.Click here to read Links
[Antidepressant effects of dopamine agonists : Experimental and clinical findings.]
[Article in German]Lemke MR.
Rheinische Kliniken Bonn, Kaiser-Karl-Ring 20, 53111, Bonn, Deutschland, mr.lemke@lvr.de.
Results of preclinical and clinical studies implicate that, in addition to serotonin and norepinephrin, dopaminergic mechanisms play a role in the pathogenesis and treatment of depression. Newer antidepressants such as bupropion, sertraline, and venlafaxine act as partial inhibitors of presynaptic dopamine reuptake. Experimental studies show that dopaminergic effects contribute to the development of anxiety, depression, and anhedonia. These studies revealed, among the new nonergot dopamine agonists, anxiolytic properties for ropinirole and anxiolytic, antidepressive, and antianhedonic effects of pramipexole which seem to relate to its specific action on D(2) and D(3) receptors in the mesolimbic system and prefrontal cortex. In addition, affective disorders may be associated with impairments of neuronal plasticity, and pramipexole seems to exert neurotrophic properties. Controlled and open studies in depressed patients with Parkinson's disease show therapeutic effects of dopamine agonists on motor deficits, anhedonia, and depression. Various dopamine agonists have been tested in open studies in patients with depression and may add to the spectrum of treatment options in mood disorders. Recently published placebo-controlled trials in small patient groups implicate that pramipexole is effective as additional treatment to mood stabilizers in I and II bipolar depression.
PMID: 17187269 [PubMed - in process]
--------------------------------------------------9: Psychopharmacology (Berl). 2000 Jul;151(1):91-7.Click here to read Links
Anxiolytic profile of ropinirole in the rat, mouse and common marmoset.
Rogers DC, Costall B, Domeney AM, Gerrard PA, Greener M, Kelly ME, Hagan JJ, Hunter AJ.Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Derek_C_Rogers@sbphrd.com
RATIONALE: Some features of Parkinson's disease are exacerbated by stress and anxiety and it is important to understand the effects of dopamine receptor agonists on measures of anxiety. The aim of this study was to assess the effects of the dopamine D2/D3 receptor agonist ropinirole in models of anxiety and depression in the rat, mouse and marmoset. RESULTS: In the rat elevated plus-maze test, ropinirole (0.01-1 mg/kg, i.p.) produced an inverted-U dose-response curve in the percentage time spent in the open arms. Compared with vehicle, ropinirole (0.1 mg/kg) had a significant anxiolytic-like effect, which was similar to that observed with 1.5 mg/kg diazepam. This effect was found at doses that did not affect motor behaviour or induce stereotypy. In the mouse black and white box test of anxiety, ropinirole (0.1-10 mg/kg, i.p.) increased both the rearing time and number of line crosses in the white section. This effect reached statistical significance for both measures at a dose of 0.1 mg/kg and suggests an anxiolytic-like action of the compound. By contrast, the dopamine agonist bromocriptine (0.1-10 mg/kg, i.p.) did not produce significant changes in these behaviours. In the marmoset human threat test, ropinirole (0.01-10 microg/kg, s.c.) reduced the number of postures at all doses tested and this reached statistical significance at 10 microg/kg. Ropinirole did not compromise the effect of amitriptyline in the Porsolt test of depression and in itself produced antidepressant-like effects. CONCLUSIONS: These data demonstrate that systemic administration of ropinirole produces anxiolytic-like effects in three separate models in the mouse, rat and marmoset. This may predict an action of ropinirole in man that would provide a superior profile of action over other presently available anti-parkinsonian agents.
PMID: 10958122 [PubMed - indexed for MEDLINE]
--------------------------------------------------10: Can J Psychiatry. 2005 May;50(6):357-60.Links
Ropinirole in treatment-resistant depression: a 16-week pilot study.
Cassano P, Lattanzi L, Fava M, Navari S, Battistini G, Abelli M, Cassano GB.Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA. pcassano@partners.org
OBJECTIVE: The study aimed to assess the antidepressant efficacy and tolerability of adjunctive ropinirole in outpatients with treatment-resistant depression (TRD). METHOD: The study sample consisted of patients with a major depressive episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5 mg daily was added to tricyclic antidepressants or selective serotonin reuptake inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and 16. We defined response as a 50% or greater reduction of the Montgomery-Asberg Depression Rating Scale (MADRS) total score plus a score of 1 ("very much improved") or 2 ("much improved") on the Clinical Global Impression of Improvement scale at endpoint. Tolerability was monitored with the Dosage Record Treatment Emergent Symptom Scale. RESULTS: Seven patients had major depressive disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was 1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%) patients were responders. Two patients discontinued ropinirole because of dizziness. CONCLUSIONS: These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated.
PMID: 15999953 [PubMed - indexed for MEDLINE]
--------------------------------------------------11: Int Clin Psychopharmacol. 2002 Nov;17(6):307-10.Click here to read Links
Ropinirole for antidepressant-induced sexual dysfunction.
Worthington JJ 3rd, Simon NM, Korbly NB, Perlis RH, Pollack MH; Anxiety Disorders Research Program.Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA. jworthington@partners.org
Sexual dysfunction is a relatively common side-effect of antidepressants, occurring in approximately one-half of patients, and is associated with significant distress and treatment non-compliance. Dopaminergic agents have been reported to be helpful for the treatment of antidepressant-induced sexual dysfunction and, in this report, we examined the efficacy of the dopamine agonist ropinirole for this indication. Thirteen patients (three women, 10 men), aged 42.6 +/- 7.7 years, who reported sexual dysfunction on a stable dose of antidepressant, were treated openly with ropinirole initiated at 0.25 mg/day and titrated up to 2-4 mg/day over 4 weeks, as tolerated. Ten of the 13 took ropinirole for at least 4 weeks, one discontinued due to an adverse event and two because of lack of response. Sexual dysfunction, as assessed by the Arizona Sexual Experience Scale scores, was reduced from 18.8 +/- 3.6 to 13.8 +/- 4.3 after 4 weeks on ropinirole at a mean dose of 2.1 mg/day. Overall, seven of 13 patients (54%) were rated as responders on the Clinical Global Impression of Improvement Scale. The addition of ropinirole may represent a potentially useful treatment strategy for antidepressant-induced sexual dysfunction.
PMID: 12409684 [PubMed - indexed for MEDLINE]
__________________________________________________
I found one study examining sleep quality in patients taking dopamine agonists, although the population sample were Parkinson's Disease patients, so that may not be relevant to psychiatric illness, but from my own experiences with dopamine agonists I'm inclined to think it is.
__________________________________________________1: CNS Drugs. 2001;15(4):267-75.Links
Sleep disorders in patients with Parkinson's disease: epidemiology and management.
Larsen JP, Tandberg E.Department of Neurology, Central Hospital of Rogaland, Stavanger, Norway.
Patients with Parkinson's disease can experience a number of sleep disorders, including insomnia, parasomnias and daytime somnolence [specifically, excessive daytime sleepiness (EDS) and sleep attacks]. Insomnia is a frequent and important complaint of patients with the disease. Both the pathology of Parkinson's disease and dopaminergic drugs may contribute to the much higher than expected frequency of sleep fragmentation and disrupted sleep among these patients. In addition, coexisting depression seems to be a major and frequent risk factor for insomnia in Parkinson's disease. After recognising a sleep problem, the first step in management is to examine and diagnose the type of insomnia and possible medical or psychological factors that may disturb nocturnal sleep. The next step is to give the patient appropriate advice on sleep hygiene. Increasing the dosage of dopaminergic drug treatment will often increase sleep disruption and should be avoided unless the patient's sleep is primarily disturbed by the motor manifestations of parkinsonism during the night. Depression should be looked for and if appropriate be treated in any patients with insomnia. If it becomes necessary to treat the patient with an hypnosedative agent, it is important to use a drug with a short half-life and that manifests as few adverse effects as possible the next morning. Up-to-date guidelines for the use of hypnosedatives should be followed. Patients with Parkinson's disease experience a wide range of parasomnias. The majority of behaviours may be related to rapid eye movement (REM) sleep behaviour disorder (RBD) or to a spectrum of symptoms ranging from vivid dreaming to psychosis. RBD is effectively treated with clonazepam. In addition, the atypical antipsychotics have given physicians new and better treatment options for psychotic symptoms in individuals with Parkinson's disease. EDS is common in Parkinson's disease, while sleep attacks seem to be rare manifestations of the disease or its treatment. Significant EDS is found in 15% of patients with Parkinson's disease compared with in 1% of healthy elderly people. Sleep attacks are observed in patients treated with all dopaminergic medications but have recently been brought to prominence because of their association with the newer dopamine agonists ropinirole and pramipexole. Patients with Parkinson's disease should be informed about the possibility of developing sleep problems during the day when prescribed new drugs. Appropriate actions with regard to driving must be taken if significant and persistent daytime somnolence or sleep attacks appear.
PMID: 11463132 [PubMed - indexed for MEDLINE]
__________________________________________________Q
poster:Quintal
thread:777910
URL: http://www.dr-bob.org/babble/20070815/msgs/778020.html