There continues to be a major drug industry push to prescribe the newer and much more expensive atypical anti-psychotic medications for all sorts of psychiatric disorders.  These medicines are much more profitable for Big Pharma.  Depression is no exception.  The push is on.  However, atypicals do not compare favorably to anti-depressants for depression, so most industry-funded studies compare them to placebo treatment.  Government has provided very little funding for independent studies, despite the fact that huge amounts of public money is going to pay for these expensive medications. 

Atypical Anti-Psychotic Inferior to Fluoxetine or Nortriptyline for SSRI and Nortriptyline Failures: In an 8 week DB study of 500 patients, who had failed to respond to an SSRI and then also failed to respond to a trial of nortriptyline during an open-label lead-in phase, these patients were randomly assigned to 1 of 4 treatment groups: olanzapine (6-12 mg/day) plus fluoxetine (25-50 mg/day) combination, olanzapine alone, fluoxetine, or nortriptyline (25-175 mg/day). MADRS depression scores decreased by 8.7 points from baseline (28.5) for the olanzapine/fluoxetine combination, 7.0 points for olanzapine alone (p = .08), 8.5 for fluoxetine alone (p = .84), and 7.5 for nortriptyline (p = .30), with no significant differences among the therapies. A post hoc analysis of a subgroup of patients who had an SSRI treatment failure during their current MDD episode (N = 314) revealed that the olanzapine/fluoxetine combination group had a significantly (p = .005) greater decrease in MADRS scores than the olanzapine group. Olanzapine/Fluoxetine Combination for Treatment-Resistant Depression: A Controlled Study of SSRI and Nortriptyline Resistance. Shelton RC, et al. Vanderbilt University and Lilly Drug Company. J Clin Psychiatry. 2005 Oct;66(10):1289-97. Ed: It appears that atypical anti-psychotics are a waste of money in treating treatment resistant depression, even when compared to using the medication with which the patients had been resistant.  Switching to bupropion, an MAO inhibitor or adding lithium, l-thyroxine, and/or folic acid might all have done better.  

Amisulpride and Acetyl-L-Carnitine Both Helped Chronic Depression: In a 12-week DB PC study of 204 patients with dysthymia, long-lasting depression, acetyl-L-carnitine (ALCAR) 500 mg b.i.d. did as well as the atypical antipsychotic amisulpride 50 mg b.i.d. with patients in both groups showing considerable improvement. A double-blind, randomised, controlled clinical trial of acetyl-l-carnitine vs. amisulpride in the treatment of dysthymia. Zanardi R, et al. Vita-Salute University San Raffaele, Milan, Italy. Eur Neuropsychopharmacol 2005 Nov 25. 

Amisulpride Helped Depression Better than Haldol or Risperidone: In three studies (n = 612) comparing amisulpride (400-800 mg/day, n = 339) with haloperidol (15-20 mg/day, n = 160) and risperidone (8 mg/day, n = 113) for schizophrenia, the anxiety/depression BPRS subscore showed a significant (P = 0.011) difference in favor of amisulpride (5.6) compared with haloperidol (4.4) and risperidone (3.7). Amisulpride provided a significantly greater improvement compared both to haloperidol and risperidone in more severely depressed patients (BPRS anxiety/depression subscore > or = 16 at baseline, P = 0.001). This significant advantage in favour of amisulpride is seen from the 2nd week of treatment. Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone. Peuskens J, et al. Universitair Centrum Sint Jozef, Kortenberg, Belgium. . Eur Neuropsychopharm 2002 Aug;12(4):305-10. Ed: Amisulpride is not available in the U.S.  It causes some weight gain, but much less than olanzapine.

Amisulpride Did as Well as Paroxetine (Paxil): In an 8-week DB study of 272 patients with major depression, amisulpride (50 mg daily) and paroxetine (20 mg daily) did equally well on HAM-D, MADRS, and CGI scores for depression. Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study. Cassano GB, et al. University of Pisa, Italy. . Int Clin Psychopharm 2002 Jan;17(1):27-32. Ed: Amisulpride also did as well as imipramine in yet another study in 1997.

Amisulpride Worked Faster than Sertraline (Zoloft): In a 12-week DB study of 313 patients with dysthymia, amisulpride (50 mg daily) did as well as sertraline (50-100 mg daily). The response rate [> 49% decrease in HAMD score] was higher with amisulpride after 4 weeks (63% vs. 50%, P < 0.02) and 8 weeks (82% vs. 69%, P < 0.009) but equally effective at week 12. Faster response on amisulpride 50 mg versus sertraline 50-100 mg in patients with dysthymia or double depression: a randomized, double-blind, parallel group study. Amore M, et al. University of Parma, Italy. Int Clin Psychopharm 2001 Nov;16(6):317-24.

Amisulpride Did as Well as Amitriptyline (Elavil): In a 6-month DB study of 250 patients with dysthymia, amisulpride 50 mg/day did as well as amitriptyline 25-75 mg/day with slightly fewer side-effects (73% versus 64% amisulpride). At least a 50% improvement in MADRS depression scores occurred in 60% and 62% of patients under amisulpride and amitriptyline, respectively. Clinical Global Impression: 67% of amisulpride and 68% of amitriptyline patients were rated as 'very much' or 'much' improved. Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline. AMILONG investigators. Ravizza L. University of Torino, Italy. J Psychopharm 1999;13(3):248-54.

Amisulpride as Good as Amineptine: Amisulpride, a selective antagonist for D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a 3-month DB PC study, amisulpride (50 mg/day) did as well as anti-depressant amineptine (200 mg/day) in the treatment of 323 patients with primary dysthymia. Amisulpride and amineptine were both superior to placebo (p < 0.0001) on the Clinical Global Impression: 63, 64 and 33% responders, respectively; improvement of Montgomery-Asberg Depression Rating Scale and Scale for the Assessment of Negative Symptoms scores following amisulpride or amineptine treatment was twice as high as with placebo (p < 0.0001). Results show that amisulpride can improve symptoms of chronic depression in dysthymia. Amisulpride versus amineptine and placebo for the treatment of dysthymia. Boyer P, et al. Paris, France. Neuropsychobiol 1999;39(1):25-32.

Amisulpride Did as Well as Fluoxetine (Prozac): In a 3-month DB study of 281 patients with dysthymia or a single episode of major depression in partial remission, amisulpride 50 mg/day did as well as fluoxetine 20 mg/day. MADRS depression scores were reduced by at least 50% in 74% of patients with amisulpride and 67% with fluoxetine. Anxiety measured by HAM-A score decreased more with amisulpride (63%) than with fluoxetine (54%; P = 0.021). Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study. Smeraldi E. University of Milan-School of Medicine, Italy. J Affect Disorder 1998 Feb;48(1):47-56.

Olanzapine Adjunct Slightly Helps Fluoxetine: DB PC 8wk 28 medication resistant patients. First treated fluoxetine 20-60mg/d in open trial. Those with HAM-D >20 after 6wk randomized to fluoxetine, olanzapine 5-20/d or combo. Combo rx did best with rapid improvement in first week to 20% decr in HAM-D, then some backsliding to 15% decrease vs little net change in other two groups. Wt gain 2#, 13#, and 14#! RC Shelton, Eli Lilly, Am J Psych 158:131-4, 1/02.

Risperidone: Case of Monotherapy for Psychotic Depression: A 33 year old Chinese woman not responding to fluoxetine + flupenthixol 6 wk or fluoxetine + trifluperazine + ECT for 5 weeks did respond while on risperidone 4mg/d in 4 days. J Clin Psych 98;59:624. Author says that previous studies support risperidone as monotherapy or adjunctive for depression. Schiz Bull 97;23:155, J Clin Psychopharm 98;18:111, same 98;18:89. Ed: Such case studies are totally worthless.  Journals like the Journal of Clinical Psychiatry, which are little more than puppets for the pharmaceutical industry, publish such reports, along with many equally misleading "open trials."  It helps the journal reap lots of lucrative industry advertising.