Section 3.1.2.2 Risperidone

General Description

Risperidone (Risperdal) is a dopamine receptor antagonist. However, this drug is distinct from all other antipsychotics, as it is also a serotonin receptor antagonist. It is a potent antagonist of the dopamine type 2 receptor; and it has additional unique pharmacological features on the serotonin type 2 receptor.

Risperidone, like the other dopamine receptor antagonists, is effective in the treatment of schizophrenia. In addition, risperidone may have clinical advantages in the treatment of the negative symptoms of schizophrenia. The drug's unique side effect profile may also offer specific treatment advantages.

Indications for Medication

Risperidone is effective in the treatment of schizophrenia and other psychotic disorders. The other psychotic disorders would include schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, manic episodes and major depressive disorder with psychotic features.

Risperidone is effective in secondary psychoses that are associated with general medical conditions such as brain tumors or substance related disorders. Risperidone is also effective in reducing the severely agitated or violent patient, and may be effective in agitation association with delirium and dementia.

In several studies, Risperidone was shown to be especially effective in reducing the negative symptoms of schizophrenia. Risperidone may be especially helpful in the therapy of treatment-resistant schizophrenia. Risperidone may be the antipsychotic to consider before initiating a Clozapine trial.

In addition, with its improved side effect profile, Risperidone may be particularly useful in those patients who are treatment resistant to other dopamine antagonists and/or those patients who have a history of adverse reactions to the traditional antipsychotic medications.

Clinical Guidelines

The therapeutic range for Risperidone is from 1-16mg a day. Most studies report the most effective Risperidone range is from 4-8mg a day with a maximum response rate at the 6mg daily dose.

Risperidone is often started at a low dose, perhaps 1-2mg a day. Risperidone can be gradually titrated to a therapeutic level around 6mg a day. Increased side effects develop with a more rapid titration schedule.

Risperidone should be maintained at the usual effective range of 4-8mg for 2-4 weeks before considering a trial at a higher dose. Some patients may take longer to respond with improvement in negative symptoms.

Adverse Effects

Risperidone is associated with significantly fewer and less severe neurological side effects than the typical dopaminergic antagonist drugs. Risperidone is associated with fewer extrapyramidal side effects and a reduced need for antiparkinson drugs.

Risperidone may be associated with anxiety, insomnia, somnolence, dizziness, constipation, nausea, dyspepsia, rhinitis, rash and tachycardia. Dose related side effects include sedation, fatigue, accommodation disturbances, orthostatic dizziness, palpitations, weight gain, diminished sex drive and erectile dysfunction.

Rare adverse reactions with long-term use of risperidone may include neuroleptic malignant syndrome, priapism, thrombocytopenic purpura and seizures in patients with concomitant hyponatremia.

Drug-Drug Interactions

Risperidone may have a wide range of drug-drug interactions similar to the other dopamine receptor antagonists. Risperidone may interact with antacids, anticholinergics, anticonvulsants, antidepressants, antihypertensives and central nervous system depressants.

Antacids and cimetidine may reduce the absorption of risperidone, reducing its efficacy. Anticholinergics may also reduce the absorption of risperidone. Cigarette smoking may decrease plasma levels of risperidone, reducing its efficacy.

Tricyclic antidepressants and risperidone may decrease each other's metabolism resulting in elevated plasma levels of both medications. The sedative and hypnotic effects of these medications may be additive. Fluoxetine may dramatically increase the level of risperidone.

Risperidone may inhibit the uptake of guanethidiene and may also inhibit the hypotensive effects of clonidine and alpha-methyldopa. Conversely, risperidone may have an additive effect on other hypotensives.

Risperidone may potentiate the CNS depressant effects of sedatives, antihistamines, opiates, opioids and alcohol. This is particularly problematic in patients with any impaired respiratory status.

The co-administration of risperidone with lithium may result in symptoms similar to those of lithium toxicity and neuroleptic malignant syndrome.