Risperidone lithium

Tricyclic antidepressants Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Antipsychotics Phenothiazines Risperidone Lithium... 

The vast majority of children with enuresis have normal uro-dynamics, including nocturnal bladder capacity. Functional bladder capacity can be estimated using this formula age in years + 2 = ounces of capacity. In some children, there appears to be a relationship between developmental immaturity (motor and language milestones) and enuresis, but the mechanism is unknown. Drugs like lithium, clozapine, risperidone,... 

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. 

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. 

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). 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

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. 

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. 

Combination therapy The combination of risperidone with lithium or valproate is indicated for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder, as defined in the DSM-IV. 

Topiramate may affect alcohol, amitriptyline, CNS depressants, lithium, oral contraceptives, digoxin, estrogens, hydantoins, metformin, risperidone, and valproic acid. 

Of the atypical antipsychotics, clozapine, olanzapine, and risperidone have been studied the most. Clozapine was used to treat 10 treatment refractory acutely manic patients and 15 schizomanic patients. Using reduction in the YMRS score as the outcome measure, 72% improved (non-rapid cycling, bipolar patients). Comparison of olanzapine (5-20 mg) with placebo showed significant reduction of the YMRS in 49% vs. 24% of subjects by 3 weeks, with significant change evident by the first week. In a trial comparing risperidone at 6 mg with haloperidol at 10 mg and low-dose lithium (800-1200 mg/day) efficacy was similar over the 28 days of the trial. 

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... 

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. 

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. 

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)... 

A 35-year-old woman who had taken lithium carbonate 800 mg/day for 2 years was also given risperidone 6 mg/ day for a manic relapse. She missed two menstrual periods and had galactorrhea. A head CT scan showed a pituitary microadenoma and the prolactin concentration was 125 pig/l (reference range up to 20 pg/1). Risperidone withdrawal resulted in disappearance of the prolactinoma. Her other symptoms persisted and did not change with olanzapine 2.5 mg/day however, bromocriptine 12.5 mg/day for 2 weeks relieved her symptoms and the prolactin concentration normalized. 

In combination with neuroleptics, especially haloperidol, there is an increased likelihood of severe encephalopathic syndromes that are sometimes irreversible (Baldessarini, 1978 Cohen et al., 1974). There is a case report of a similar reaction from combining lithium with the newer neuroleptic, risperidone (Swanson et al., 1995). 

Swanson, C., Jr., Price, W., 8c McEvoy, J. (1995). Effects of concomitant risperidone and lithium treatment. American Journal of Psychiatry, 152, 1096. 

Of 39 patients taking lithium, 18% had neutrophilia and 15% had raised activity of polymorphonuclear elas-tase (a marker of granulocyte activation) (345). In keeping with these observations, a chart review of 38 patients taking clozapine showed an increase in leukocyte count when lithium was added (42). A man with olanzapine-induced neutropenia (with a prior history of risperidone-induced neutropenia), which normalized with drug withdrawal, had no difficulty when the drug was reintroduced after the patient had been treated with lithium (43). 

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. 

There were no changes in lithium pharmacokinetics when risperidone was substituted open-label for another neuroleptic drug in 13 patients (634). On the other hand, an 81-year-old man had an acute dystonic reaction 4 days after lithium was added to a regimen of risperidone, valproic acid, and benzatropine (635). 

---