Mood Stabilizers risperidone

First, initiate and/or optimize mood-stabilizing medication lithium3 or valproate3 or atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone)... 

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). 

First, optimize current mood stabilizer or initiate mood-stabilizing medication lithium,0 valproate,0 or carba-mazepine0 Consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Alternative medication treatment options carbam-azepine0 if patient does not respond or tolerate, consider atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) or oxcarbazepine. 

Mood stabilizers (e.g., lithium, valproic acid, and carbamazepine) used as augmentation agents may improve labile affect and agitated behavior. A placebo-controlled trial supports fast symptom improvement when divalproex is combined with either olanzapine or risperidone. 

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. 

In the Expert Consensus survey (Rush and Frances, 2000), respondents were asked to rate which classes of medication may be helpful for treating patients with severe and persistent physical aggression and those who destroyed property. The atypical antipsychotics were rated most highly, followed by anticonvulsant/ mood stabilizer. These were followed (with much lower priority) by antidepressants and beta-blockers. Among the atypical antipsychotics, risperidone was rated most highly, followed by olanzapine others had much lower ratings. Divalproex or valproic acid and carbamazepine were rated highest of the mood stabi-... 

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. 

Although the data are relatively limited, we believe that risperidone may be a potential mood-stabilizing agent, and that lower doses and a slower escalation can substantially reduce any risk of a switch in mood phases (93). 

Approximately 50 subjects were randomized to each group. Open lithium or VPA treatment was also used. Those patients treated with risperidone or haloperidol had a substantially greater decrease from baseline YMS scores than those on placebo (i.e., 14 for risperidone and 13 for haloperidol versus 8 points for the placebo group (p=0.009). Further, 57% of the risperidone group achieved at least a 50% decrease from the YMS baseline score, compared with 38% in the placebo group. This study demonstrates that the addition of risperidone or haloperidol produced a better response than that achieved with a mood stabilizer alone. 

In fact, with more moderate-to-severe episodes, a mood stabilizer alone is usually insufficient, and initial treatment often requires a concurrent antipsychotic, preferably a novel agent. In these situations, we advocate using an initial lower-dose schedule (e.g., risperidone 1 to 4 mg/day olanzapine 2.5 to 10 mg/day). If primary mood stabilizers are ineffective or not tolerated, evidence indicates that monotherapy with agents such as olanzapine or risperidone may be effective. 

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. 

Recent case reports have suggested that atypical antipsychotics may also benefit patients with PTSD. For example, low doses of risperidone in combination with an antidepressant or mood stabilizer were reported effective for nightmares and flashbacks in patients with treatment-refractory PTSD ( 292). Both clozapine and olanzapine have also been reported to reduce PTSD symptoms in patients with a co-morbid psychotic disorder ( 293, 294). Finally, olanzapine added to fluoxetine resulted in significant improvement of hyperarousal symptoms in a patient with treatment-refractory PTSD caused by severe childhood physical and sexual abuse (295). 

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. 

Other classes of medications that may be used for pediatric insomnia include mood stabilizers/anticonvulsants (depakote), other classes of antidepressants (mir-tazapine), atypical antipsychotics (risperidone), and chloral hydrate, as well as herbal... 

Fountoulakis KN, et al. Report of three cases that received maintenance treatment with risperidone as a mood stabilizer. Ann Gen Hosp Psychiatry 2004 3(1) 10. 

In a 6-week open study of risperidone (mean dosage 4.7 mg/day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3% were completely symptom-free (35). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n = 13), exacerbation of mania ( n = 5), drowsiness (n = 3), and impotence (n = 2). 

Nevertheless, risperidone has been used in the treatment of mania in combination with mood stabilizers (SEDA-23, 69) (SEDA-26, 64). 

Risperidone may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy... 

Antidepressants mirtazapine, nefazodone, sertraline Neuroleptics thioridazine, haloperidol, clozapine, quetiapine, risperidone, sertindole, ziprasidone Mood stabilizers carbamazepine, gabapentin, lamotrigine... 

Quantifying blood levels of those compounds for which assays are available is an easy and reliable method to ensure compliance and assess metabolic status. Reliable assays are currently available for compounds such as nortriptyline, clozapine, olanzapine, risperidone, and all the mood stabilizers. 

Yatham LN, Grossman F, Augustyns I, et al. Mood stabilizers plus risperidone or placebo in the treatment of acute mania. Br J Psychiatry 2003 182 141-147. 

Clinical experience with various pharmacological regimens (mainly mood stabilizers) has suggested that a drug that is efficacious in one manifestation of mania is not necessarily the treatment of choice for the overall spectrum of manic states. Much progress have been made in the treatment of acute manic states, especially since the demonstrated efficacy of the second-generation antipsychotics (e.g. olanzapine, quetiapine, and risperidone) for the treatment of acute mania. However, treatment of acute manic states remains incomplete, and new treatment strategies are in continuous development. ... 

Sachs G, Grossman F, Okamoto A et al. Risperidone plus mood stabilizer versus placebo plus mood stabilizer for acute mania of bipolar disorder a double-blind comparison of efficacy and safety. Am j Psychiatry 2002, 159 1146-1154. 

Benabarre A, Vieta E, Colom F et al. Treatment of mixed mania with risperidone and mood stabilizers. Can j Psychiatry 2001 46 866-867. 

---