Risperidone mania

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

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. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Risperidone (Risperdal). Risperidone is also approved by the FDA for the treatment of acute mania. It acts as an atypical antipsychotic at doses up to 4-6mg/day. Over this dose, and at lower doses in children and the elderly, risperidone acts more like a typical antipsychotic in that extrapyramidal side effects are common. 

Choice of a Mood Stabilizer. With the advance of atypical antipsychotics and an ever-expanding list of anticonvulsants, the number of medications reported to treat acute mania and hypomania continues to grow. In fact, all of the atypical antipsychotics, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole have FDA approval for the treatment of acute mania. Long-term protection against future episodes of illness has also been demonstrated with several of these agents, which can influence the choice of initial therapy. 

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). 

Freeman TW, Clothier JL, Pazzaglia P, et al A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry 149 108-111,1992 Frenchman IB, Prince T Clinical experience with risperidone, haloperidol, and thioridazine for dementia-associated behavioral disturbances. Int Psychogeriatr 9 431-435, 1997... 

Mood Disorders. Risperidone has also been reported to benefit major depressive disorder with psychosis, bipolar mania, and schizoaffective disorder ( 83, 84, 85, 86 and 87). 

In contrast, other reports have indicated that risperidone may have precisely the opposite effect in bipolar and schizoaffective patients, with good-to-excellent mood-stabilizing and antipsychotic effects noted and no emergent cases of mania or hypomania. Tohen and coworkers (91), for example, effectively treated 20 bipolar I patients with a mean risperidone dosage of 5.1 1.6 mg/day for more than 6 weeks with no induction of mania. Madhusoodanan and colleagues ( 92) also reported on two elderly schizoaffective, bipolar type, and two elderly bipolar patients who received a mean risperidone dosage of 1.9 0.9 mg/day for about 3 weeks with a good response and no induction of mania or hypomania. 

Janicak et al. (87) studied the relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder. Sixty-two patients (29 depressed type, 33 bipolar type) entered a randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). They found no difference between risperidone and haloperidol in the amelioration of psychotic and manic symptoms nor any significant worsening of mania with either agent. For the total PANSS, risperidone produced a mean decrease of 16 points from baseline, compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively and for the CARS-M mania factor, 3 and 7 points, respectively. 

Dwight MM, Keck PE, Stanton SP, et al. Antidepressant activity and mania associated with risperidone treatment of schizoaffective disorder. Lancet 1994 344 554-555. 

Stoll AL. Risperidone induction of mania fact or fallacy Int Drug TherNews11996 31 5-6. 

Dwight et al. (291) reported their experience with risperidone in eight patients with schizoaffective disorder (six bipolar type two depressive type). All six bipolar type patients showed the onset of or an increase in mania shortly after starting risperidone (mean number of treatment days = 7 3 mean dose = 7 1 mg/day). In this context, O Croinin et al. (292) reported on a chronic paranoid schizophrenic patient who was admitted in an acute psychotic state unresponsive to thioridazine or CPZ. Risperidone was started (6mg/day by day 3), but by the end of the first week she was displaying hypomanic symptoms. When risperidone was discontinued and haloperidol introduced, her hypomanic symptoms resolved. 

Goodnick (293) reported on two acutely bipolar manic patients who had not responded to or could not tolerate lithium but did respond favorably to risperidone. The author also hypothesized that risperidone s ability to block 5-HT 2 receptors may make this agent useful for treating both mania and psychotic depression. 

Sachs et al. (294) reported the results of a double-blind, randomized trial of acute mania. Patients were treated with risperidone, haloperidol, or placebo. 

Goodnick PJ. Risperidone treatment of refractory acute mania [Letter]. J din Psychiatry 1995 56 431-432. 

The introduction of novel antipsychotics such as risperidone and olanzapine has led to a series of case reports and controlled trials regarding their use for patients with mania, whether complicated by psychotic symptoms or not (384, 492, 493). Singh and Catalan (494), for example, found risperidone helpful in four male AIDS patients who were also experiencing a manic phase of their schizoaffective disorder. Notably, low doses (i.e., 1 or 2 mg twice daily) seemed sufficient. 

Lane HY, Chiu WC, Chang WH. Risperidone monotherapy for mania and depression. Am J Psychiatry 1999 156 1115. 

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. 

Risperdal has a particular tendency to produce adverse stimulant effects, including insomnia, agitation, and anxiety. Probably because of these stimulant effects, it may have an increased risk of causing mania (Dwight et al., 1994). Stimulation may also account for risperidone-induced... 

Q9 Alternative drugs used to treat mania include benzodiazepines, carba-mazepine or antipsychotic agents such as fluphenazine and risperidone. 

Pavuluri MN, Henry DB, Carbray JA, Sampson G, Naylor MW, Janicak PG. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Dis 2004 82S S103-11. 

Yatham LN, Binder C, Kusumakar V, Riccardelli R. Risperidone plus lithium versus risperidone plus valproate in acute and continuation treatment of mania. Int Clin Psychopharmacol 2004 19 103-9. 

Mania has rarely been associated with classic neuroleptic drugs, but has been described in patients treated with new antipsychotic drugs, especially risperidone (SEDA-22, 69). Several cases of mania, presumably associated with olanzapine, have been reported (99,137-144). The mechanism is not clear. It has been suggested that olanzapine could lead to manic symptoms in patients with schizophrenia because of its potent anti-5HT2A action. 

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