Complications
A subjective sensation of restlessness reported by patients. Management options for patients who have akathisia associated with antipsychotic therapy include: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, or adding a beta-blocker.[9]
Postural hypotension, due to anticholinergic or alpha-1 adrenoceptor blockage by antipsychotic medicine, is often present at the initiation of medication or after an increase in dosage.[183]
This complication is often transitory in the first hours or days of treatment. Older people are particularly susceptible, as are patients in the dose-titration phase of clozapine therapy, and those with peripheral vascular disease, diabetes with pre-existing autonomic neuropathy, or compromised cardiovascular function. When severe, orthostatic hypotension can cause syncope, dizziness, or falls.[9][184] Precautionary measures include patient education to assume an upright position slowly. Supportive measures include use of support stockings, increased dietary salt, and optimised fluid intake. Slower dose titration, decreasing or dividing doses of antipsychotic medication, or switching antipsychotic may be required.[9]
Dystonia is an involuntary muscular contraction of any striate muscle. Dystonia is common with high-potency antipsychotic medications (e.g., haloperidol, fluphenazine) and can be life-threatening if associated with laryngospasm.[9] Patients who have acute dystonia associated with antipsychotic therapy should be treated with an anticholinergic medication.[9] Intravenous or intramuscular diphenhydramine or benzatropine produce reversal of dystonia in minutes.[185]
Can occur at any time in the first few months after start of medicine or with an increase in the dose of antipsychotic medication.[9] The characteristic symptom constellation includes: autonomic dysfunction, muscular rigidity, hyperthermia, and altered consciousness. It is imperative NMS is diagnosed early as it is life-threatening.[9] Besides immediate drug discontinuation and intravenous fluids, patients need supportive interventions, preferably in an intensive care unit.[186]
Parkinson's-like clinical picture with postural stiffness, lack of movement fluency, small steps, and limited facial expressions. Diphenhydramine or benzatropine is given daily at the start of treatment, especially when starting a first-generation antipsychotic, to decrease the risk of parkinsonism.[187] Management options for patients who have parkinsonism associated with antipsychotic therapy include: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, or treating with an anticholinergic medication.[9]
As many as one third of patients with schizophrenia use illicit drugs at any time.[190] Substance use may precede the disease debut or develop during the course of the illness.
Patients with schizophrenia smoke more heavily than the general population, and present with higher morbidity and mortality from smoking-related illnesses.[191] Bupropion may decrease the amount of tobacco use and increase abstinence rates in smokers with schizophrenia, without affecting the stability of their symptoms.[191]
Characterised by repetitive, involuntary, purposeless movements. The Abnormal Involuntary Movement Scale is a very useful tool for early detection of tardive dyskinesia and for ongoing monitoring.[192] Higher risk with high-potency antipsychotic medications.[193] Patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy may benefit from a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2).[9]
Closely correlated with schizophrenia and suicidal tendencies. Treatment with antidepressant medicine may be indicated with close evaluation for risk of suicide. Depressive symptoms that occur during an acute episode of psychosis often improve as psychotic symptoms respond to treatment.[9]
Some antipsychotics, such as clozapine and olanzapine, are more likely than others to cause weight gain.[194] If a weight gain of 5% occurs, a medicine change should be considered.[195]
Adding topiramate or metformin, or switching from a drug with high weight gain potential to a drug with a lesser weight gain risk (e.g., zipraszidone) might be an effective weight control intervention while providing for stability of schizophrenia symptoms.[196][197][198][199]
In addition, exercise combined with nutritional advice can be beneficial.[196]
Waist circumference, blood pressure, fasting glucose, and lipid panel should be monitored.[9][200] Patients can remain on a medicine causing metabolic abnormalities only when a risk-benefit assessment is done and the metabolic adverse effect is controlled.[201] Switching from a drug with high risk for a metabolic syndrome (e.g., olanzapine) to a drug with a lesser metabolic risk (e.g., quetiapine or ariprazole) might be an effective metabolic intervention while providing for stability of schizophrenia symptoms.[199]
Symptoms can be divided into peripheral (e.g., dry mouth, constipation, blurred vision, urinary retention) and central (e.g., delirium, impaired learning and cognition).
Patients usually develop tolerance to adverse effects such as dry mouth; rinsing with water or chewing sugarless gum may help. For blurred vision, a temporary reduction of the medicine dosage may be indicated. If acute urinary retention or delirium occurs, antipsychotic medicine needs to be discontinued. If constipation develops, initial treatment can include stool softeners or osmotic laxatives.[9] Anticholinergic adverse effects are often dose-related and may improve with lowering of the dose or administering the medications in divided doses.[9]
Antipsychotic medicine with higher dopamine blockade (e.g., haloperidol, fluphenazine, and risperidone) can cause elevated prolactin, leading to galactorrhoea, changes in libido, gynaecomastia, irregular menstrual cycle or amenorrhoea in women, and erectile or ejaculatory dysfunction in men.[9][202] Clinicians should remain alert for these effects and screen for possible symptoms at each clinic visit; prolactin levels should be checked if clinically indicated. Decreasing the dose of medication or switching to an alternative may be necessary. Limited evidence suggests that adding aripiprazole may have a prolactin-lowering effect.[203]
Adjunctive treatment with sildenafil and aripiprazole can improve sexual dysfunction and/or decrease prolactin levels.[204][205] Administration of a dopamine agonist such as bromocriptine may also be considered.[9]
QT prolongation, T-wave flattening, and torsades de pointes has been reported to occur with antipsychotic use.[206] A baseline ECG may be required, particularly if there are cardiac risk factors, such as a personal or family history of cardiac disease (conduction abnormalities and/or structural cardiac abnormalities).[207]
Agranulocytosis has been reported with most antipsychotic medicines. Clozapine can decrease the number of neutrophils and at times can lead to severe neutropenia. One meta-analysis suggested an incidence of severe neutropenia, defined as blood levels of absolute neutrophil count (ANC) <500/microlitre, in 0.9% of patients treated with clozapine, with a case fatality rate for individuals with severe neutropenia of 2.1%. For clozapine-treated patients as a group, the incidence of death due to severe neutropenia was 0.013%.[208]
Only patients treated with clozapine require routine ANC monitoring. In the UK, ANC monitoring is recommended weekly for 18 weeks, then every 2 weeks for the rest of the first 12 months, then every 4 weeks thereafter.[209] However, monitoring recommendations may vary in other countries (e.g., in some countries, weekly monitoring is recommended for the first 6 months) and you should consult your local guidelines.
Approximately 20% to 30% of patients with schizophrenia have symptoms that are considered resistant to treatment.[113]
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment-resistant.[210]
Clozapine should be considered for patients who have not had an adequate response to a trial of two different antipsychotics; this should only be started by a specialist.[2][68][114]
If clozapine is ineffective or partially effective, augmentation strategies should be considered.[1][2] However, these are highly specialist and should be used with caution.
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