Many More Drugs for Depression

This section is for rarely used medications with limited usefulness for depression.  Most are on the buttons on the left, but mifepristone, modafanil (Provigil), sildenafil (Viagra), and pramipexole (Mirapex) are below.

Choline No Benefit for Rapid Cycling Bipolars in Small Study: In a very small 12-week DB PC study of 8 patients on lithium, 50 mg/kg/day of choline bitartrate had no significant effect on CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels. Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy. Lyoo IK, Demopulos, CM et al. Harvard-McLean. Bipolar Disord. 2003 Aug;5(4):300-6.

Mifepristone is a glucocorticoid receptor antagonist.  It has been used on the theory that the high cortisol levels found in severe mood disorders may be causing some of the problem.

Mifepristone Helped Psychotic Depression in Very Small Study: Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day DB PC crossover study. No adverse effects were not observed or reported. All five showed substantial improvements in their Hamilton  Depression scores while they were receiving mifepristone, and four of five showed substantial improvement in their Brief Psychiatric Rating Scale scores. Little improvement was seen with placebo. Rapid reversal of psychotic depression using mifepristone. Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF. Stanford University. J Clin Psychopharmacol. 2001 Oct;21(5):516-21

Mifepristone Helped Psychotic Depression in Small Study: In a random assignment open trial of 30 psychotically depressed patients, they received 50 mg, 600 mg, or 1200 mg of mifepristone for 7 days. Side effects were mild and sporadic. Of 19 subjects in the combined 600- and 1200-mg group, 13 had a 30% or greater decline in their Brief Psychiatric Rating Scale (BPRS) scores, compared with 4 of 11 in the 50-mg group. In the 600- and 1200-mg group, 12 of 19 subjects showed a 50% decline in the BPRS positive symptom subscale, a more sensitive index for the symptoms seen in PMD, compared with 3 of 11 in the 50-mg group; 8 of 19 subjects in the 600- and 1200-mg group had a 50% decline in the HAMD-21, compared with 2 of 11 in the 50-mg group. An open label trial of C-1073 (mifepristone) for psychotic major depression. Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF. Biol Psychiatry. 2002 Sep 1;52(5):386-92

Mifepristone Helped Bipolar Depression in Small Study: 20 bipolar patients were treated with 600 mg/day of mifepristone (RU-486) for 1 week in a DB PC crossover design. Over the total 6 weeks of the study, spatial working memory performance was significantly improved compared to placebo (19.8% improvement over placebo). Measures of verbal fluency and spatial recognition memory were also improved after mifepristone. Hamilton Depression scores were significantly reduced compared to baseline (mean reduction of 5.1 points). No significant change occurred after placebo. Improvements in Neurocognitive Function and Mood Following Adjunctive Treatment with Mifepristone (RU-486) in Bipolar Disorder. Young AH, Gallagher P, Watson S, Del-Estal D, Owen BM, Nicol Ferrier I. University of Newcastle upon Tyne, UK. Neuropsychopharmacology, 5 May 2004

Modafanil (Provigil) was approved by the FDA as an "orphan drug" for narcolepsy.  This meant that the manufacturer was given some regulatory breaks enabling less money to be spent on its development because it was aimed at helping a rare disease.  Since then, the manufacturer has been trying to promote it for a very wide range of diseases and a few doctors have been prescribing it very frequently and at a very high cost.  It is a very expensive drug with very limited usefulness in my opinion.

Harvard, Pittsburgh Push Modafinil for Drug Company Despite Study Documenting Very Little Benefit: In a multicenter 8-week DB PC study of 311 patients with major depression and only partial responses to SSRI therapy after at least 8 weeks, half were given the expensive brandname stimulant modafinil 200 mg/day, an "orphan" drug approved only for the treatment of narcolepsy. There was no significant improvement in 31-item or 17-item HAM-D depression scores, Epworth Sleepiness scores, Fatigue Severity scores, Brief Fatigue Inventory scores, or MADRS depression scores. More side-effects occurred with modafinil (nausea and jitteriness).  The only significant finding favoring modafinil and only at final visit, modafinil improved patients' overall clinical condition compared with placebo on the basis of Clinical Global Impressions-Improvement scores (p = .02). The authors claim, that based on their study, "these findings suggest that modafinil is a well-tolerated and potentially effective augmenting agent for SSRI partial responders with fatigue and sleepiness." A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. Fava M, Thase ME, DeBattista C. MGH-Harvard and University of Pittsburgh. Ed: The company manufacturing modanifil has a long history of funding very brief, even single dose studies, to irresponsibly push its drug.  This study actually has a good research design and found nothing. The CGI is the most unreliable of all research measures. It could easily be influenced just by the fact that patients like the little amphetamine like surge you get after taking modafinil.  That doesn't mean its good for you.  Harvard and the University of Pittsburgh have long histories of cranking out studies for drug companies. 

Modafanil (Provigil) Helps Fatigue Barely and Briefly at Great Cost: In a 136-patient DB PC of Major Depression, modafanil or placebo was added to standard anti-depressants during the daytime at 100-400 mg once a day.  While researchers from Stanford claim that modafanil "rapidly improved" fatigue and daytime sleepiness by the second week, in fact, despite the relatively large size of the study, its superiority over placebo was only at p<.05!  Any advantage over placebo had totally disappeared by week 6.  Modafanil had no beneficial effect on depression scores. The study was financed by the manufacturer! 

Sildenafil (Viagra): While it is extremely expensive ($10 a pill), there is a single report that Viagra might help depressed and impotent men.

Sildenafil DB Helps Depressed at Urological Clinic for Impotence: Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life. DB of 152 for 12 weeks. Am J Psychiatry 2001 Oct;158(10):1623-30; 152 men 56yo aver with both depression NOS and impotence with HAM-D > 12 rx 100 mg/d or less with 90% improved sex with sildenafil vs. 12% in controls. 76% had >50% decline in HAM-D vs 14% controls!

Pramipexole (Mirapex): The dosage used in the only study reported would cost around $70 per month.

Pramipexole (Mirapex) Helped Bipolar Depression in Very Small Study: In a 22-patient DB PC study with pramipexole, a dopamine agonist usually used to treat Parkinson's disease, those on up to 1.7 mg/day had a much larger drop in depression over the 6 week period. All patients were on a mood-stabilizer. One became hypomanic. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Goldberg JF, Burdick KE, Endick CJ. Am J Psychiatry. 2004 Mar;161(3):564-6