Risperidone dosage

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. 

In a report of 122 elderly patients on risperidone, hypotension was noted in 28.7% and symptomatic orthostatic hypotension was noted in 9.8%. Significant decreases in blood pressure occurred with risperidone treatment (p = 0.0001) and were common in patients with cardiovascular disease and those taking an SSRI or valproate (p = 0.03) (502). Hence, like other antipsychotics, risperidone should be prescribed cautiously for elderly patients and those with preexisting cardiac disease. Its hypotensive versus its orthostatic hypotensive effects may be an age-related pharmacodynamic response. Blood pressure, including orthostatic blood pressure, should be monitored routinely until the risperidone dosage is stabilized. Furthermore, when risperidone therapy is initiated in the elderly, dosage should be titrated from 0.25 to 0.5 mg two times a day with increments of 0.25 to 0.5 mg weekly (92). 

Lane H-Y, Chang Y-C, Cheng Y-C, Liu G-C, Lin X-R, Chang W-H. Effects of patient demographics, risperidone dosage, and clinical outcome on body weight in acutely exacerbated schizophrenia. J Clin Psychiatry 2003 64 316-20. 

Brody AL. Acute dystonia induced by rapid increase in risperidone dosage. J Clin Psychopharmacol 1996 16(6) 461-2. 

Visual distortion with generalized anxiety and panic attacks has been attributed to risperidone (SEDA-22, 69). Visual disturbance resembling hallucinogen persistent perception disorder occurred after each of three consecutive risperidone dosage increases in a 55-year-old woman there was absence of substance abuse (129). 

Lane H-Y, Chang Y-C, Chiu C-C, Lee S-H, Lin C-Y, Chang W-H. Fine-tuning risperidone dosage for acutely exacerbated schizophrenia clinical determinants. Psychopharmacology 2004 172 393-9. 

It would seem important to monitor the levels of risperidone and 9-hy-droxyrisperidone in patients given carbamazepine, being alert for the need to raise the risperidone dosage, possibly by as much as two-thirds. 

Usual dose Administer on a once-daily schedule, starting with 2 to 3 mg/day. Adjust dosage at intervals of not less than 24 hours and in dosage increments/decrements of 1 mg/day. Risperidone doses higher than 6 mg/day were not studied. 

Do not combine 2 different dosage strengths of risperidone injection in a single administration. 

Case Example Because of a patient s partial response to 5 months of clozapine therapy at 600 mg/day, risperidone was added for augmentation (started with 0.5 mg b.i.d. and increased to 1 mg b.i.d. after 1 week). Before this addition, the clozapine plasma level was 344 ng/mL, but after 2 weeks of risperidone augmentation, the level was elevated to 598 ng/mL with no adverse effects and substantial clinical benefit. In another report, there was an increase in the steady-state plasma levels of clozapine (675 mg/day) and its active metabolite norclozapine after the addition of risperidone 2 mg/day in a patient treated for 2 years. Before the addition of risperidone, her clozapine and norclozapine levels were 829 and 1,384 ng/mL, respectively. Two days after risperidone was added, these levels rose to 980 and 1,800 ng/mL. Clozapine dosage was reduced to 500 mg/day, and after 5 days of combined treatment with 4 mg/day of risperidone, the clozapine and norclozapine levels were 110 and 760 ng/mL, respectively. Aside from some mild oculogyric crises, she had no symptoms of clozapine toxicity or clinical changes during the period of cross-tapering. In another case, risperidone was added to clozapine because the patient had relapsed after discontinuation of fluphenazine and had not responded to clozapine. The addition of risperidone resulted in an acute remission of psychosis ( 100). 

Galactorrhea has been reported in relation to risperidone (SEDA-25, 69 SEDA-26, 65 SEDA-27, 63), and four new cases have been published (1036). It is suggested that this condition can occur after many weeks of risperidone treatment, with small dosages (2-4 mg/day), and at times even after drug withdrawal. 

Catastrophic deterioration, with the severity of obsessive-compulsive symptoms returning to pretreatment levels, was observed in a 21-year-old man when risperidone was added to fluoxetine in a dosage that was stepped up to 3 mg/day (53). 

A 40-year-old man had taken clozapine 450 mg/day and risperidone 6 mg/day for several years. Nefazodone 200 mg/day was added in an attempt to improve persistent negative symptoms, and after a week the dosage was increased to 300 mg/day. One week later, he reported anxiety and dizziness and was hypotensive. The combined concentrations of clozapine and its active metabolite norclozapine had increased from 309 ng/ml before nefazodone to 566 ng/ml. The nefazodone dosage was reduced to 200 mg/day and the anxiety, dizziness, and hypotension resolved over the next 7 days. At the same time plasma concentrations of clozapine and norclozapine fell to 370 ng/ml. 

A 26-year-old woman with bipolar I disorder took lithium and valproate, and sometimes additional risperidone and lamotrigine. Both risperidone and lamo-trigine produced dermatological adverse effects. Her serum lithium concentration was 0.82 mmol/1. Topiramate 75 mg/day was added. A week later, she continued to show a mixed state with mostly manic features and a raised lithium concentration of 1.24 mmol/1. The lithium concentration continued to increase over the next 4 days to 1.97 mmol/1 even though the lithium dosage was reduced from 900 to 750 mg/day. Lithium was withdrawn and the lithium concentration fell. Lithium was then restarted at half the admission dose to achieve a blood concentration of 0.67 mmol/1. Subsequent increases in the dose of topiramate resulted in further increases in the lithium concentration. 

The results of one of the clinical trials in which olanzapine (Eli Lilly) was compared with risperidone (Janssen Pharmaceutica) (SEDA-22, 64) gave rise to a debate between researchers of the two pharmaceuticals companies on some of the possible flaws (100-105). Since the modal dosage over the 28-week trial was 7.2 mg/day, significantly higher than that used in actual clinical practice (average dose 4.6 mg/day), the higher incidence of risperidone-associated adverse effects could have been explained by this dosage difference. 

Several studies have shown a relation between neuroleptic drug dosages, extrapyramidal adverse effects, and the degree of dopamine D2 receptor occupancy (SEDA-18, 48) (181,182). Atypical neuroleptic drugs, such as olanzapine, quetiapine, risperidone, and sertindole, which have lower affinities for D2 receptors, cause fewer extrapyramidal effects than typical neuroleptic drugs (183,185,186). However, there are reports of extrapyramidal effects associated with these atypical neuroleptic drugs (187-189). 

---