Risperidone bipolar disorder

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Depot antipsychotics (e.g., haloperidol decanoate, fluphenazine decanoate, and risperidone long-acting injection) can be used for maintenance therapy of bipolar disorder with noncompliance or treatment resistance. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Risperidone Benzisoxazole 0.25-10 High 2 Bipolar disorder Conduct disorder PDD Psychotic disorders Tic disorders Frazier et ah, 1999 Findling et ah, 2000a McDougle et ah, 1997 Armenteros et ah, 1997 Lombroso et ah, 1995... 

Frazier, J.A., Meyer, M.C., Biederman, J., Wozniak, J., Wilens, T.E., Spencer, T.J.,Kim, G.S., and Shapiro, S. (1999) Risperidone treatment for juvenile bipolar disorder a retrospective chart review./ Am Acad Child Adolesc Psychiatry 38 960-965. 

Chart reviews and open trials of outpatients with bipolar disorder and bipolar spectrum disorder have been published for 28 risperidone- and 23 olanzapine-treated treated children and adolescents (Frazier et ah, 1999 2001). Significant decreases in mania, depression, and aggression ratings occurred over the course of treatment however, other medications were also used simultaneously. Additional anecdotal information exists for olanzapine (Soutullo et ah, 1999 Chang and Ketter, 2000), quetiapine (Schaller and Behar, 1999), and clozapine (Fuchs, 1994). 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

Madhusoodanan S, Brenner R, Araujo L, et al. Efficacy of risperidone treatment for psychoses associated with schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia in 11 geriatric patients a case series. J din Psychiatry 1995 56 514-518. 

Ghaemi SN, Sachs GS, Baldassano CF, et al. Acute treatment of bipolar disorder with adjunctive risperidone in outpatients. Can J Psychiatry 1997 42 196-199. 

Sachs G, Bowden C, Chou J, et al. Risperidone versus placebo as combination therapy to mood stabilizers in the treatment of the manic phase of bipolar disorder focus on efficacy. Presented at the American Psychiatric Association Annual Meeting, Chicago, May 13-18, 2000. 

Frazier JA, Meyer MC, Biederman J, etal. Risperidone treatment for juvenile bipolar disorder a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999 38 960-965. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Fig. 11—40) and clinical features, not only as compared with clozapine (Fig. 11 — 37) but also as compared with risperidone (Fig. 11—39)- Olanzapine is atypical in that it generally lacks EPS, not only at moderate doses but usually even at high doses. Thus, olanzapine tends to be used for some of the most difficult cases of schizophrenia, bipolar disorder, and other types of psychosis in which good control of psychosis without EPS is still desired, yet aggressive treatment is required. On the other hand, this approach can be very expensive. 

Risperidone 118 has been used to treat schizophrenia and bipolar disorder <1997WO042940>. Piperidine derivatives such as panamesine 119, a 1,4,4-trisubstituted piperidine, and preclamol 120, a 1,3-disubstituted piperidine, have also been used as antipsychotic agents . 

The benefits of the atypical neuroleptic drugs in patients with bipolar disorder and the possibility that risperidone, quetiapine, olanzapine, and clozapine cause... 

In an 8-week study, pre-school-age children with bipolar disorder (aged 4-6 years) took either olanzapine (n = 15 mean age 5.0 years 10 boys mean dose 6.3 mg/day) or risperidone (n = 16 mean age 5.3 years 12 boys mean dose 1.4 mg/day) (59). There were significantly more dropouts with olanzapine (6 versus 1), including one patient who withdrew because of adverse events (increased appetite and hand tremor). The main adverse events, found with both treatments, were significant increases in prolactin concentrations and weight gain. With both treatments, increased appetite, flu-like symptoms, headaches, and sedation were the most commonly reported adverse effects. 

Biederman J, Mick E, Hammerness P, Harpold T, Aleardi M, Dougherty M, Wozniak J. Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children. Biol Psychiatry 2005 58 589-94. 

The efficacy and safety of risperidone have been examined in special groups of patients, such as those with psychotic depression (4), autistic disorders (41), bipolar disorder (5), mental retardation (6), and children and adolescents (7). 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

Patients with bipolar disorder may benefit from risperidone, but this conclusion has mostly come from open studies with small sample sizes (SEDA-23, 69). Experience with risperidone has been reviewed with data from Canadian studies (34). 

A 30-year-old man with a history of bipolar disorder had substantial weight gain with olanzapine and was switched to risperidone (dose unknown) and lithium carbonate (450 mg bd) (112). A few days later he developed confusion, mild muscle rigidity, a raised temperature, and increased creatine kinase activity. The medications were withdrawn and he responded to supportive therapy. 

A 21-year-old woman with a 2-year history of bipolar disorder stopped all of her medication when she discovered that she was pregnant she was given risperidone 2.5 months after childbirth, gradually increasing... 

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