Anti-psychotics have always been used and found helpful in treating and preventing manic episodes.  Of course, American psychiatry has largely abandoned traditional anti-psychotics with the primary good reason being an apparent higher rate of tardive dyskinesia, a hard to treat movement side-effect.  However, the real reason is the massive advertising promotion of the very expensive atypicals.  Many bipolar patients are now treated with an atypical anti-psychotics, which can be effective especially for the acute manic phase.  However, they are not of major benefit for treating depressive moods, although there is some evidence of benefit.  My favorites are ziprasidone (Geodon) and aripiprazole (Abilitat) because of their lack of weight gain, diabetes, and increased risk of death with olanzapine (Zyprexa) and, to a lesser extent, quetiapine (Seroquel).  Geodon (80 mg for most patients) once a night is much less expensive than any of the others, but must be taken with a snack in order to aid absorption.  For all anti-psychotic patients, I give magnesium 250 mg. twice a day in order to decrease the risk of cardiac arrhythmias, hypertension, and diabetes.

Virtually all of the below studies were funded by the manufacturer of the atypical.  This means that their reports will be designed and worded so as to make the manufacturer's medication look as good as possible and that any studies where the atypical did not do well will never be published and will be hidden as well as possible.

Aripiprazole Appeared to Do Much Better for Mania than Haloperidol: In a 12-week aripiprazole manufacturer-funded DB study of 347 acute manic or mixed bipolar I patients, patients on aripiprazole were much more likely to have a full response to treatment that those taking haloperidol (50% vs. 28%; P < 0.001). However, at week 12, 51% of aripiprazole, but only 29% of haloperidol patients were still on their medication. Extrapyramidal adverse events were much more frequent with haloperidol than aripiprazole (63% v. 24%). Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. Vieta E, et al. University of Barcelona, Spain. Br J Psychiatry. 2005 Sep;187:235-42. Ed: Based on extensive research on manufacturer financed research, this study should be viewed with a great deal of caution.  One wonders how well the EPS side-effects were managed and whether psychiatrists were more quick to discontinue the study medication if EPS side-effects were present.  If this latter were true, it would definitely stack the deck in favor of the manufacturer's aripiprazole.  Also, many psychiatrists don't use the full range of superior treatments for EPS.  For example, very few use amantidine despite extensive research in its favor. 

Aripiprazole (Abilitat) Helps Acute Mania: Like many other atypical anti-psychotic manufacturers, the makers of aripiprazole have funded a study showing its medicine helps patients with acute mania more than placebo.  Quite a number of older studies demonstrated that traditional anti-psychotics achieve the same result.  A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. 3 week DB PC 262 manic patients. A 50% decrease on the Young Mania Rating Scale was achieved in 40% vs. 19% with placebo. Keck PE Jr, Marcus R, Tourkodimitris S, Ali M, Liebeskind A, Saha A, Ingenito G; Aripiprazole Study Group.

Aripiprazole did Better than Haldol for Mania: In a 12 week DB PC of 347 patient with aripiprazole 15 mg/d or 30 mg/d vs. haldol 10-15 mg/d, aripiprazole did better because of a high haldol dropout rate due to extrapyramidal side-effects. Sanchez R, Bourin M, Auby P, et al. Aripiprazole vs. haloperidol for maintained treatment effect in acute mania. Program and abstracts of the Fifth International Conference on Bipolar Disorder; June 12-14, 2003; Pittsburgh, Pennsylvania. Abstract P174. (Ed: In the old days, such dropout rates were uncommon and if EPS couldn't be managed on haloperidol, there are many other traditional anti-psychotics which work just as well but have much lower EPS rates.  Indeed, haloperidol has one of the highest EPS rates for a traditional anti-psychotic. A more fair design would allow patients having to stop haldol to switch to another traditional anti-psychotic with the outcome reported.  In fact, aripiprazole doesn't have the tardive dyskinesia risks of the traditionals, but is no better for mania.)

Haldol as Good as Olanzapine (Zyprexa) for Acute Mania: Two DB PC studies of 453 patients treated for 6 weeks with haloperidol 3-15 mg/d or olanzapine 5-20 mg/d found no significant difference in the percentage of patients recovered (46% vs. 52%). Haldol had more EPS and olanzapine had a 6# weight gain vs. none for haldol. Lilly. A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania. Tohen M, Goldberg JF, et al. Arch Gen Psychiatry. 2003 Dec;60(12):1218-26

Haldol as Good as Risperidone (Risperdal) for Acute Mania: In a 12-weel DB PC trial of 438 patients with acute bipolar mania, those who received received 1-6 mg/day of risperidone or 2-12 mg/day of haloperidol took an average of 4.2 mg/day of risperidone and 8.0 mg/day of haloperidol during the initial 3-week phase and 4.1 and 7.4 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone or haldol than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Smulevich AB, Khanna S, et al. National Mental Health Research Center, Moscow, Russia. 

French Journal Editorial Not Impressed by Olanzapine Research: (1) Lithium reduces the number of relapses and suicide attempts. (2) Olanzapine is the first neuroleptic to be approved in France for prevention of relapse in bipolar disorder. Many neuroleptics are already used for this indication but their efficacy has not been established. (3) One DB PC study of 361 patients who were treated just after recovering from a manic episode was supposed to last 48 weeks, but only 146 patients were treated for more than 8 weeks. Therefore, the trial results, including an observed effect on mania, cannot be interpreted to imply long-term prevention. (4) One double-blind trial compared olanzapine plus a mood stabiliser with placebo plus a mood stabiliser in 344 patients who had recovered from an acute episode. Only 21 patients completed the 12-month trial, and the percentage of patients who had relapses (manic or depressive) did not differ significantly between the groups. (5) In a third double-blind trial, 431 patients in remission from a manic episode after treatment with olanzapine + lithium were treated for 12 months with lithium or olanzapine. This trial suggested that olanzapine was more effective in preventing depressive and manic relapses (30% of patients, compared to 38.8% with lithium), but only 171 patients completed the trial. Most dropouts were due to adverse events (19% with olanzapine, 26% with lithium). The impact of treatment on suicide risk was not studied. (6) In a fourth study, 101 patients in remission from a mixed or manic episode continued their initial treatment with olanzapine or sodium divalproate in double-blind manner for 11 months. The risk of relapse was not significantly different between the groups, but the study sample size was too small to tell whether or not the treatments were equally effective. (7) Trials focusing on prevention of relapse in patients with bipolar disorder confirmed the known adverse effects of olanzapine, including weight gain and QTc prolongation. Olanzapine was associated with more weight gain and sedation than lithium. Hyperglycaemia occurring on olanzapine can cause life-threatening ketoacidosis. (8) Lithium remains the standard treatment for preventing recurrent bipolar disorder. There is no firm evidence that olanzapine is more effective than a mood stabiliser after lithium failure, or that it boosts the efficacy of lithium. Olanzapine: new indication. Prevention of bipolar disorder: unconvincing trials. Prescrire Int. 2005 Aug;14(78):140-2.

Olanzapine Did as Well as Lithium in Manic/Mixed Patients: In a study of bipolar (manic/mixed) patients with two or more manic or mixed episodes within 6 years, and a YMRS score >19 received open-label co-treatment with olanzapine and lithium for 6-12 weeks. The 431 in symptomatic remission (YMRS <13; 21-item Hamilton depression <9) were randomly assigned to 52 weeks of DB monotherapy with olanzapine, 5-20 mg/day  or lithium (0.6-1.2 meq/liter). Relapse (score > 14 on either the YMRS or Hamilton depression scale) occurred in 30% of olanzapine and 39% of lithium patients. Depression relapse occurred in 16% of olanzapine and 11% of lithium patients. Weight gain with olanzapine (4 pounds gain) was worse than with lithium (3 pound loss). Only 171 completed the study, mainly due to side-effects of both medicines. Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial. Tohen M, Calabrese JR, et al. Lilly Research Laboratories, Indianapolis. . Am J Psychiatry. 2005 Jul;162(7):1281-90. Ed: Olanzapine is very expensive, causes a lot of weight gain and some diabetes, and may not help the more common bipolar, depressed patient.

Olanzapine: Anti-Psychotic with Lithium or Valproate Lowers Risk of Relapse: In a DB PC 18-month trial of Bipolar I patients achieving a remission of mania on olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml), half had the olanzapine replaced by placebos. The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023). Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. Tohen M, Chengappa KN, et al. Lilly Drug Company. Br J Psychiatry. 2004 Apr;184:337-45

Olanzapine Better than Lithium in Questionable Drug Company Study: Mauricio Tohen,  Harvard, 5th International Conf. on Bipolar Disorders. 543 bipolar I patients, manic or mixed, with two manic or mixed episodes in last six years with mania scores of 20 or higher (YMRS) received an open-label combination of olanzapine and lithium for 6-12 weeks. Remission was achieved by 431, who were then randomized in a double-blind to monotherapy of olanzapine 5-20 mg/d or lithium 0.6-1.2 mEq/L for 52 weeks. More olanzapine patients finished the trial — 46.5% vs. 32.7%. Relapse to depression or mania: 30.0% of olanzapine and 38.8% of lithium patients (P = .055). Manic episodes were lower with olanzapine (14.3% vs. 28.0%, P < .001). Depressive relapses were equal (16.1% vs. 15.4%; P = .895). Discontinuation due to adverse events: 18.9% (olanzapine) vs. 25.7% (lithium); P = .105). Olanzapine patients gained slightly more weight (1.79 kg vs. 1.38 kg; P < .001). 5th ICBD: Abstract P201. 6/13/03 (Ed: I don't like the discontinuation studies that drug companies have started funding. I'm not sure that they prove what is claimed. Also, while atypicals are effective at treating and avoiding mania, bipolar patients die from suicides during depressions, not during manias.  Lithium markedly decreases bipolar suicide compared to valproate. Patients above were chosen to stress mania. Before we use atypical monotherapy for Bipolar Disorder, as recommended by the authors, we need to know what the suicide rate will be compared to lithium.) Funded by Eli Lilly.

Olanzapine May Have Anti-Depressant Effect: In a secondary analysis of a 6-week DB PC study of olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes, in the dysphoric subgroup (n=85) mean HRSD depression score improvement was significantly greater in olanzapine co-therapy patients than in those receiving placebo plus lithium or valproate (P<0.001). Substantial contributors to this superiority included the HRSD suicide item (P=0.001). Total Young Mania Rating Scale improvement was also superior with olanzapine co-therapy. Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania. Baker RW, Brown E, et al. Lilly Corporate Center, Indianapolis, IN. Br J Psychiatry. 2004 Dec;185:472-8.

Olanzapine Helped Mania in DB: 139 acute mania DB PC 5-20mg/d. Amer J Psych 99;156:702

Olanzapine did as Well or Better than Divalproex in DB: 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. 248 pt Eli Lilly trial. 54% vs. 42% response. 5# vs. 2# wt gain. Olanzapine versus divalproex in the treatment of acute mania. Tohen M, Baker RW, et al. Am J Psychiatry 2002 Jun;159(6):1011-7

Olanzapine did as Well as Lithium in Acute Mania: 30 acute manic admissions were treated in DB study with 10 mg/d olanzapine or only lithium 400 BID (a below average dose). Both groups very similar improvement. Berk, U Witwatersrand, Int Clin Psychoph 99;14:339

Olanzapine Helped Mania in DB: 115 pt DB PC YMRS > 19, 4 weeks. Olanzapine started at 15mg. and titrated to 5-20/d. Greater than 50% response in 65% of olanzapine vs. 43% placebo. Depression worsened in 11% olanzapine vs. 18% placebo.

Olanzapine Add-On Benefit to Lithium/Valproate: 6 wk DB PC 344 bipolar manic or mixed with inadequate improvement on two weeks of lithium or valproate alone. Olanzapine improved YMRS vs. monotherapy (-13.11 vs. -9.10; P = .003). Response (> or = 50% improvement on YMRS) (67.7% vs. 44.7%; P< .001). Olanzapine improved (HAMD-21) (4.98 vs. 0.89 points). Eli Lilly, Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Tohen M, Chengappa KN, et al. Arch Gen Psychiatry 2002 Jan;59(1):62-9

Olanzapine did Better than Haldol in DB: Eli Lilly study 219 manics DB 12 weeks. At week 12, olanzapine treatment maintained the significantly favorable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. Int Clin Psychopharmacol 2002 Sep;17(5):227-37

Olanzapine Alone Inadequate for Bipolar Depressed: Sanjay Dube of Eli Lilly studied 833 bipolar depressed in a PC DB of olanzapine vs. olanzapine + fluoxetine vs. placebo. At one week, MADRS score decreased 9.55 for the combination vs. 8.31 olanzapine alone vs. 5.08 for placebo (P < .001). However, persistent responders were 32.4% for the combo vs. olanzapine alone 18.3% (P < 0.05) or placebo (12.7%; P < .001) groups. Persistent responders = responded within two weeks and did not relapse. 5th ICBD: Abstract P52. Presented June 12, 2003.

No Value to Continuing Anti-Psychotic After Mania Remission?: In a very small DB PC study of 37 patients in acute mania, patients were treated with lithium, carbamazepine, or valproate and also perphenazine, a traditional anti-psychotic.  After, the mania remitted, all patients continued their mood stabilizer and patients either continued the perphenazine or were switched to placebo. After 6 months, the data showed no benefit to continuing the perphenazine.  Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients. Zarate CA Jr, Tohen M. Am J Psychiatry. 2004 Jan;161(1):169-71.

Quetiapine (Seroquel) Patients Usually Undermedicated, But High Cost Eats Up Savings: Using a health plan database of patients with bipolar disorder or schizophrenia treated with quetiapine monotherapy for at least four consecutive months, commercially insured patients with schizophrenia (n = 581) or bipolar disorder (n = 2421) received quetiapine monotherapy at average daily doses of 237 mg and 147 mg, respectively. For schizophrenia, mental health charges decreased by $1.28 for each additional milligram of quetiapine (P = 0.1097). For bipolars, they decreased by $1.31 per additional milligram (P = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each additional milligram of quetiapine (P = 0.0189). Relationship between initial quetiapine dose and effectiveness as reflected in subsequent mental health service use among patients with schizophrenia or bipolar disorder. Gianfrancesco F, et al. Montgomery Village, MD. . Value Health. 2005 Jul-Aug;8(4):471-8. Ed: Unfortunately, Seroquel is so expensive at $.99 per mg per month (Walgreens.com 10/15/05), that increasing the dose is not cost-effective. Geodon is much more cost-effective and the preferred first-line choice. 

Quetiapine Did Well Compared to Placebo for Depression: In an 8-week DB PC study of 542 outpatients with bipolar I or II disorder experiencing a major depressive episode (DSM-IV), quetiapine (600 or 300 mg/day) at either dose was significant better on MADRS depression scores for a 50% response at 8 weeks : 58% and 57%, respectively, vs. 36% for placebo and remission (MADRS < or =12) were 53% vs. 28% for placebo. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Calabrese JR, et al. Case University, Cleveland, OH. . Am J Psychiatry. 2005 Jul;162(7):1351-60.

Quetiapine Helped as Add-On to Lithium or Divalproex: In 2 DB PC studies of 402 manic patients randomized to 3 or 6 weeks, those receiving quetiapine plus lithium or divalproex did better than those on lithium or divalproex alone (YMRS decrease of 15.29 vs. 12.19; p<.05). The average quetiapine dose in responders was 492 mg/d. More QTP + Li/DVP-treated patients completed the trial, and there was no difference in discontinuation rates due to adverse events between the two groups. Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania. Yatham LN, Paulsson B, et al. University of British Columbia. J Clin Psychopharmacol. 2004 Dec;24(6):599-606.

Quetiapine Did No Better than Lithium for Mania: In a 12-week DB PC study of 302 patients with bipolar I mania, quetiapine (72/107) and lithium (67/98) groups were more likely to complete the study than the placebo group (35/97). Quetiapine and lithium did equally well. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. Bowden CL, Grunze H, et al. University of Texas Health, San Antonio. J Clin Psychiatry. 2005 Jan;66(1):111-21. Ed: Lithium is much, much less expensive.  The tremor and insomnia side-effects are easily treated.  While it sometimes causes weight gain, quetiapine was much worse than lithium (7# vs. 2#). Quetiapine levels tended to increase to an average of 618 mg/d at the end. Lithium levels were at the low end averaging 0.8 MEq/L.  

Quetiapine Helps as Adult Adjunct for Mania: Three-week PC DB study of 191 patients in bipolar I mania by Jamie Mullen of AstraZeneca Pharmaceuticals added quetiapine (100-800 mg/d) to patients already on lithium or divalproex. Quetiapine decreased mania better (YMRS)(-13.76 vs. -9.93; P = .021) with more responding (54% vs. 33%; P = .005) and remitting (YMRS 12 or less) (46% vs. 26%; P = .007). Quetiapine had no anti-depressant effect: MADRS scores (-3.36 vs. -2.79) nor prevented emergent depression (MADRS of >17 with an increase >3 at any two consecutive assessments (17% vs. 14%; P = .469). More side-effects with quetiapine: somnolence (40% vs. 10%), headache (27% vs. 21%), dry mouth (19% vs. 4%), asthenia (11% vs. 3%), posturnal hypotension (11% vs. 3%), dizziness (10% vs. 6%). Drop-out rate greater with placebo (51% vs. 39%). Quetiapine averaged 580 mg in responders, with 59% at 600 mg or more. 5th ICBD: Abstract P139. 6/12/03. Sachs G, et al. Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. Bipolar Disord 2004: 6: 213-223. Ed: This study is further proof of the long known effect of anti-psychotics working faster to bring mania under control than lithium or divalproex alone. I prefer ziprasidone on cost grounds but quetiapine is a good, but very expensive atypical medication. 

Quetiapine Helped Mania as Well as Haldol: A PC DB 12 week study of 302 bipolar manic found 61% quetiapine patients 50% better at 12 weeks vs. 39% placebo. Brecher M, Huizar K. Quetiapine vs. placebo for acute mania associated with bipolar disorder (STAMP 1). Program and abstracts of the Fifth International Conference on Bipolar Disorder; June 12-14, 2003; Pittsburgh, Pennsylvania. Abstract P27

Quetiapine as Good as Lithium or Haldol in DB for Mania: A 12 week PC DB of 604 bipolar I manics found 61% quetiapine patients responding vs 39% of placebo. Lithium and haloperidol each did as well. Jones M, Huizar K. Quetiapine monotherapy for acute mania associated with bipolar disorder (STAMP 1 and STAMP 2). Program and abstracts of the Fifth International Conference on Bipolar Disorder; June 12-14, 2003; Pittsburgh, Pennsylvania. Abstract P95

Quetiapine Helped as an Adjunct to Divalproex in Teens in DB: DB PC 30 12-18yos bipolar I manic or mixed, 6 weeks. All on divalproex. Quetiapine started 20/kg/d up to 450mg/d titration. 53% divalproex responded vs. 87% combo. Univ. Cincinnati, A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. Delbello MP, Schwiers ML, Rosenberg HL, Strakowski SM. J Am Acad Child Adolesc Psychiatry 2002 Oct;41(10):1216-23

Risperidone Better than Placebo for Mania or Mixed: In a very short manufacturer funded 3-week DB PC study of 291 adults done in India, 42% of patients on risperidone (1-6 mg/d) had remissions of their bipolar I mania or mixed state vs. 13% for placebo (p < .0001). Symptomatic remission in patients with bipolar mania: results from a double-blind, placebo-controlled trial of risperidone monotherapy. Gopal S, et al. Johnson & Johnson Pharmaceutical. . J Clin Psychiatry. 2005 Aug;66(8):1016-20.

Risperidone = Haldol Adjunct to Mood Stabilizer: 182 manic or mixed in 3 week DB PC of lithium/divalproex with haldol/risperidone/placebo. 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol. Sachs, MGH, Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Sachs GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL. Am J Psychiatry 2002 Jul;159(7):1146-54

Risperidone: Another Study Documents That Anti-Psychotics Rapidly Decrease Mania: In a 259-patient 3-week DB PC study of acute mania, risperidone averaging 4.1 mg/day decreased mania considerably more than placebo (-10.6 vs. -4.8) with most of the benefit occurring by the end of the third day (-6.8 of the -10.6 decrease in mania rating). Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial. Hirschfeld RM, Keck PE Jr, et al. University of Texas. Am J Psychiatry. 2004 Jun;161(6):1057-65. Am J Psychiatry. 2004 Jun;161(6):1057-65. 

Risperidone Better than Placebo: A 279 bipolar I mania PC DB 3 week study reported that 56% risperidone (1-6mg/d) and 42% placebo patients finished the study. Hirschfeld R, Keck P, Karcher K, Kramer M, Grossman F. Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, randomized, double-blind, placebo-controlled trial. Program and abstracts of the Fifth International Conference on Bipolar Disorder; June 12-14, 2003; Pittsburgh, Pennsylvania. Abstract P84.

Risperidone Said Better than Placebo: Another 3 week bipolar mania PC DB study with an average dose of 5.6 mg/d. Khana S, Vieta E, Lyons B, Grossman F, Kramer M. Risperidone monotherapy in acute bipolar mania. Program and abstracts of the Fifth International Conference on Bipolar Disorder; June 12-14, 2003; Pittsburgh, Pennsylvania. Abstract P219

Risperidone Better than Placebo in Child Disruptive Behavior Disorders in DB: Disruptive behaviour disorders in children averaging 8 years old were treated with 3.4 mg risperidone/day in a 6 week PC DB study of 118 children with low IQs. Using the Nisonger Child Behaviour Rating Form (N-CBRF), risperidone had 42% drop in depression and 35% in mania vs. 25% mania and 16% depression placebo decreases (p= 0.014 and p=0.001). Risperidone had better decreases in "crying, tearful" (p< 0.05), "irritability" (p< 0.001), and "feels worthless or inferior" (p< 0.001). Eric Mink, Joe Biederman, Harvard, October 27, 2003, Annual meeting of the American Academy of Child and Adolescent Psychiatry.

Risperidone = Haldol in Schizoaffective, Better if Depressed: 62 patients (29 depressed type; 33 bipolar type) DB 6-week risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Janicak, U Ill Chicago, J Clin Psychopharmacol 2001 Aug;21(4):360-8

Ziprasidone: Used for Acute Mania: 210 patients were randomly assigned in a 2:1 ratio to 3 weeks of double-blind treatment with ziprasidone (40-80 mg twice daily). Ziprasidone did better than placebo. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Keck PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K. Am J Psychiatry 2003 Apr;160(4):741-8. Ed: This is a disappointing study since no active comparator medication was used in addition to the placebo. Geodon is still my favorite, although more research wouldn't hurt. J Clin Psychopharmacol. 2005 Aug;25(4):301-10 appears to be another report of the same study.