Gepirone
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Gepirone for Depression: Very Unimpressive

 

Gepirone is a relative of buspirone.  It has been around for 21 years (the first article was published in 1983), but has never been marketed.  It is a 5HT1A receptor partial agonist.   A drug company, Organon, is now planning to market a patented extended release variety which will allow it to have a patent on the drug for many years to come.  The extended release drug reportedly causes fewer side-effects but does not appear to work any better than the immediate release version. 

 

Neither with immediate nor extended release drug look very impressive to me, although the psychiatrists doing research for the drug company have been raving about the new version.  Gepirone-ER (extended release) will probably be somewhat useful but unreasonably expensive and only of value to patients not responding to many less expensive and more powerful alternatives.  Organon hopes to be marketing the drug this year, 2004, if the FDA approves.  I can predict that many physicians will be persuaded by drug reps to use the drug.  Organon is hardly doing any great public service slightly modifying an old drug and selling it at high prices. 

 

Buspirone is available as a generic.  It was marketed for anxiety and has never been very popular although it doesn't cause many side-effects, is inexpensive, and is not addictive.  Clinical experience has been that it is not as effective as other alternatives, although for those who get benefit from it, its definitely worthwhile.

 

Gepirone-IR Said to Help Depression: A University of Pennsylvania discontinuation study found gepirone-immediate release to be better than placebo.  While I much dislike this type of research design, it appears to be becoming more common. Seventy individuals who improved while on gepirone in a 6-week open trial of up to 90 mg/day were put into a 6-week DB PC trial in which those having gepirone discontinued became more depressed than those remaining on gepirone. Side-effect drop-outs on gepirone were a high 33% during the 12 weeks. Sustained efficacy of gepirone-IR in major depressive disorder: a double-blind placebo substitution trial. Amsterdam JD, Brunswick DJ, Gibertini M. J Psychiatr Res. 2004 May-Jun;38(3):259-65.

 

Gepirone-ER Inferior Medication Pushed by Harvard Researchers for Drug Company; Slightly Better than Placebo: In an 8-week, DB PC study of 133 major depression patients with high levels of anxiety, the extended-release version of gepirone was found to be slightly better than placebo. Gepirone caused a statistically significant (p <.05) reduction in mean HAM-D-17 depression scores compared with placebo-treated patients. A statistically significant but weak effect (p <.05) in favor of gepirone ER was observed in mean change from baseline in HAM-D-17 total scores and for HAM-D factor I (anxiety/somatization) scores from week 2 onward.  Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder. Alpert JE, Franznick DA, Hollander SB, Fava M. Harvard-MGH. J Clin Psychiatry. 2004 Aug;65(8):1069-75.

 

Gepirone-ER Slightly Better than Placebo: In a DB PC 6-week study, 39% responded (50% decrease in depressive symptoms) while on gepirone-extended release vs. 25% while on placebo. Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder. Feiger AD, Heiser JF, Shrivastava RK, Weiss KJ, Smith WT, Sitsen JM, Gibertini M. J Clin Psychiatry. 2003. Mar;64(3):243-9.  Ed: While the authors, apparently funded by the manufacturer, don't point this out, this study means that seven patients would have to be treated for each patients who responds thanks to gepirone.  While this is acceptable scientifically, gepirone is no magic bullet.

 

Gepirone-IR Not Much Benefit in Anxiety Study: In a DB PC study of generalized anxiety disorder by the University of Pennsylvania, patients on diazepam (Valium) did much better than those on gepirone who had a high drop-out rate. By the 6th week, gepirone was better than placebo. Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled trial. Rickels K, Schweizer E, DeMartinis N, Mandos L, Mercer C. J Clin Psychopharmacol. 1997 Aug;17(4):272-7

 

Gepirone-ER as Good as Imipramine: In an 8-week, 123-patient DB PC study of Major Depression, gepirone (10-60 mg/day) did as well as imipramine (50-300 mg/day) and both did better than placebo.  There were more side-effects with imipramine. A double-blind comparison of gepirone extended release, imipramine, and placebo in the treatment of outpatient major depression. Feiger AD. Ed: It is almost certain that this is an industry funded study.

 

Gepirone-ER High Dose Better: In an 8-week, 145-patient DB PC study of Major Depression, gepirone (10-50 mg/day) low dose did not do as well as gepirone (20-100 mg/day) high dose. The higher dose did better than placebo. A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients. Wilcox CS, Ferguson JM, Dale JL, Heiser JF. Psychopharmacol Bull. 1996;32(3):335-42

 

Gepirone-IR Helps Atypical Depression: In an 8-week, DB PC study of 59 patients with atypical depression, 62% of patients on gepirone 10-40 mg three times a day responded (50% decrease in depression) vs. 20% responding while on placebo. New York State Psychiatric Institute. Gepirone treatment of atypical depression: preliminary evidence of serotonergic involvement. McGrath PJ, Stewart JW, Quitkin FM, Wager S, Jenkins SW, Archibald DG, Stringfellow JC, Robinson DS. J Clin Psychopharmacol. 1994 Oct;14(5):347-52. Ed: This is too small of a study to put much confidence in the results.  Still, it is interesting.  Atypical depression has been shown in more than one study to respond better to MAO inhibitor anti-depressants.  Maybe gepirone will be found to help atypical depression (excess sleep, excess appetite, hypersensitivity) better.

 

Gepirone-IR Helps Non-Melancholic, Non-Severe Depression: In a University of Pennsylvania study, patients with depression improved on gepirone, but melancholic and severely depressed patients did much less well. Gepirone, a selective serotonin (5HT1A) partial agonist in the treatment of major depression. Amsterdam JD. Prog Neuropsychopharmacol Biol Psychiatry. 1992 May;16(3):271-80

 

Gepirone-IR Helps in Two Drug Company DB Studies: Two DB PC studies show the efficacy of gepirone in the treatment of major depression. The first showed gepirone's superiority over placebo in an 8-week acute treatment of patients with major depression, including the melancholic subtype at 5-30 mg/day. Study 2 revealed benefits of gepirone compared with placebo in 4-week continuation therapy of patients with major depression who initially responded to 6 weeks of open therapy with gepirone. J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):77S-85S; Psychopathology. 1989;22 Suppl 1:27-36

 

Gepirone Used for Anxiety in Irresponsible Report: In a University of Pennsylvania open trial of just 10 patients, some benefits were claimed. Gepirone in anxiety: a pilot study. Csanalosi I, Schweizer E, Case WG, Rickels K. J Clin Psychopharmacol. 1987 Feb;7(1):31-3. Ed: The publication of such studies is simply irresponsible.  The study proves absolutely nothing, and yet the researchers make favorable claims and clinical psychiatrists and physicians will hear the claims and not look at the fact that there really was no study.  It is an embarrassment to me to see my alma mater publish such material.  Shame on the Journal of Clinical Psychopharmacology.  Don't tell the world until you have something honest to say.