Pharmacotherapy in Psychotic Disorders

Antipsychotic drugs Treat the symptoms of the disorder Do not cure schizophrenia Include two major classes: – Dopamine Receptor Antagonists – Serotonin-Dopamine Antagonists

Dopamine Receptor Antagonists Effective in the treatment of schizophrenia, particularly the positive symptoms (e.g. delusions). Shortcomings: – Only a small percentage of patients are helped enough to recover a reasonable amount of mental functioning – Associated with both annoying and serious side effects, including: akathisia and parkinsonianlike symptoms of rigidity and tremor. Potential side effects: – Tardive dyskinesia and neuroleptic malignant syndrome

Serotonin-Dopamine Antagonists Produce minimal or no extrapyramidal symptoms Interact with different subtypes of dopamine receptors than do the standard antipsychotics Affect both serotonin and glutamate receptors. Produce fewer neurological and endocrinological adverse effects Effective in treating negative symptoms of schizophrenia (e.g. withdrawal) than the typical dopamine receptor antagonist antipsychotic agents.

Approved SDAs Risperidone Clozapine Olanzapine Sertindole Quetiapine Ziprasidone

Risperidone Effective antipsychotic medication Mild side effects; not associated with extrapyramidal symptoms Causes less sedation and fewer anticholinergic effects than dopamine receptor antagonists First line agent for first break, mildly to moderately ill patients and for severely ill, treatment refractory patients

Clozapine Most effective for severely-ill patients Risk of significant adverse effects, which are not found in other SDAs. Associated with agranulocytosis, requiring weekly monitoring of neutrophil count. High risk for seizures and has significant anticholinergic effects. Useful for patients refractory to any other antipsychotic drug and for patients with tardive dyskinesia.

Olanzapine Effective medication for treatment of schizophrenia Mild profile of adverse effects, different from those of Risperidone. Less likely to produce extrapyramidal symptoms More likely to produce weight gain, orthostatic hypotension, and constipation. Useful first line agent

Sertindole Effective agent with transient adverse effects Must be slowly titrated upward to avoid orthostatic hypotension May cause sinus tachycardia, nasal congestion, and decreased ejaculatory volume Causes little weight gain and does not cause anticholnergic symptoms Ideal for poorly-compliant patients (half life of 3 days).

Quetiapine Effective No increased risk of extrapyramidal symptoms Main adverse effects include sedation, tachycardia, weight gain and agitation. Initial doses must be titrated upward to avoid orthostatic hypotension and syncope

Ziprasidone Effective Potential additional benefits for patients with affective symptoms, because it blocks reuptake of serotonin and norepinephrine, and for patients with anxiety because it is an 5-HT1A receptor agonist. Adverse effects include sedation, nausea, dizziness, and lightheadedness.

Therapeutic Principles Clinicians should carefully define the target symptoms to be treated. An antipsychotic that has worked well in the past for a patient should be used again. In the absence of such information, the choice of an antipsychotic is usually based on the adverse effect profile

Therapeutic Principles Minimum length of antipsychotic trial us 4 to 6 weeks at adequate dosages. If the trial is unsuccessful, then a different antipsychotic drug, usually from a different class, can be tried. In general, the use of more than one antipsychotic medication at a time is rarely, if ever, indicated. Patients should be maintained on the lowest possible effective dosage of medication.

Other Drugs Combination therapy with one of these drugs and an adjuvant medication may also be tried. These are: – Lithium – Anticonvulsants – Benzodiazepines

Lithium May be effective in reducing symptoms of psychosis in up to 50% of patients with schizophrenia. Usually added with an antipsychotic drug the patient is already taking A reasonable drug to try in patients who are unable to take any of the antipsychotic medications. Effective in schizophrenia patients with mood swings.

Anticonvulsants Carbamazepine or valproate used in combination with lithium or an antipsychotic Reduce episodes of violence in some schizophrenia patients

Benzodiazepines May exacerbate the severity of psychosis after withdrawal of the drug Lorazepam is preferred over diazepam because it is shorter acting and has less abuse potential.

Other Biological Therapies Electroconvulsive therapy – Catatonic patients – Patients who cannot for some reason take antipsychotic drugs Psychosurgery – No longer considered an appropriate treatment. – It is however practiced on a limited experimental basis for severe, intractable cases.