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-adrenergic blocking agent.[65]
Postural hypotension, due to anticholinergic or alpha-1 adrenoceptor blockage by antipsychotic medication, is often present at the initiation of medication or after increase in dosage.[65][275]
This complication is often transitory in the first hours or days of treatment. Older people are particularly susceptible to postural hypotension, as are patients in the dose-titration phase of clozapine therapy or those with peripheral vascular disease, diabetes with preexisting autonomic neuropathy, or compromised cardiovascular function. When severe, orthostatic hypotension can cause syncope, dizziness, or falls.[65][228] Supportive measures include use of support stockings and increased dietary salt and fluid intake. Slower dose titration, decreasing or dividing doses of antipsychotic medication, or switching to an alternative antipsychotic may be required.[65] Patients should be counseled to assume upright positions slowly as a precautionary measure. As a last resort, administration of the salt/fluid-retaining corticosteroid fludrocortisone to increase intravascular volume may be required.[65][276][277] For patients who are receiving concomitant antihypertensive treatment, adjustments to the dose of these medications may be needed.[65]
Dystonia is an involuntary muscular contraction of any striated muscle. Dystonia is common with high-potency antipsychotic medications (e.g., haloperidol, fluphenazine) and can be life-threatening if associated with laryngospasm.[65] Patients who have acute dystonia associated with antipsychotic therapy should be treated with an anticholinergic medication.[65] Intravenous or intramuscular diphenhydramine or benztropine produce reversal of dystonia in minutes.[278]
Can occur at any time in the first few months after start of medication or with an increase in the dose of antipsychotic medication.[65] 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.[65] Beside immediate drug discontinuation and intravenous fluids, patients need supportive interventions preferably in an intensive care unit.[279]
Parkinson-like clinical picture with postural stiffness, lack of movement fluency, small steps, and limited facial expressions. Diphenhydramine or benztropine is given daily at the start of treatment, especially when starting a typical antipsychotic, to decrease the risk of parkinsonism.[280] 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.[65]
Suicidal ideation tendency is one of the most dangerous complications of schizophrenia.[69] The lifetime risk of suicide is approximately 5%.[70][71][72] The risk of suicide is highest at the onset of the illness. Approximately 20% of patients with schizophrenia attempt suicide at least once and many more have significant suicidal ideation.[1]
As many as one third of patients with schizophrenia use illicit drugs at any time.[272] 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.[273] The high prevalence of smoking in patients with psychosis might be explained by the ameliorating effect of nicotine on cognitive symptoms. Bupropion may decrease the amount of tobacco use and increase abstinence rates in smokers with schizophrenia, without affecting the stability of their symptoms.[273]
Characterized 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.[224] Higher risk with high potency antipsychotic medications.[274] Patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy should be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2).[65]
Closely correlated with schizophrenia and suicidality. Treatment with antidepressant medication may be indicated with close evaluation for suicidality. Depressive symptoms that occur during an acute episode of psychosis often improve as psychotic symptoms respond to treatment.[65]
Some antipsychotics, such as clozapine and olanzapine, are more likely to cause weight gain than others.[281] If a weight gain of ≥5% occurs, a medication change should be considered.[282]
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., ziprasidone), might be an effective weight control intervention while providing for stability of schizophrenia symptoms.[163][283][284][285]
In addition, exercise combined with nutritional advice can be beneficial.[283]
Adverse effects related to metabolic syndrome are common and include weight gain, hyperlipidemia, and glucose dysregulation, including development of diabetes mellitus.[65] Fasting glucose and lipid panel should be monitored.[286] Patients can remain on a medication causing metabolic abnormalities only when a risk-benefit assessment is done and the metabolic adverse effect is controlled.[287] Switching from a medication with high risk for a metabolic syndrome (e.g., olanzapine) to a drug with a lesser metabolic risk (e.g., aripiprazole) might be an effective metabolic intervention while providing for stability of schizophrenia symptoms.[285]
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 dry mouth; rinsing with water or chewing sugarless gum may help. For blurred vision, a temporary reduction of the medication dosage may be indicated. If acute urinary retention or delirium occurs, antipsychotic medication needs to be discontinued. If constipation develops, initial treatment can include stool softeners or osmotic laxatives.[65] Anticholinergic adverse effects that do occur are often dose-related and may improve with lowering of the dose or administering the medications in divided doses.[65]
Antipsychotic medication with higher dopamine blockade (e.g., haloperidol, fluphenazine, risperidone), can cause elevated prolactin, leading to galactorrhea, gynecomastia, changes in libido, irregular menstrual cycle or amenorrhea in women, and erectile or ejaculatory dysfunction in men.[225] 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.[226]
Adjunctive treatment with sildenafil and aripiprazole can improve sexual dysfunction and/or decrease prolactin levels.[288][289] Administration of a dopamine agonist such as bromocriptine may also be considered.[65]
QT prolongation, T-wave flattening, and torsades de pointes have been reported to occur with antipsychotic use.[290] 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.[291]
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/microliter, 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%.[292]
Enrolling into a national safety program and monitoring blood levels of ANC are required in patients taking clozapine. The baseline ANC must be at least 1500/microliter for the general population, and at least 1000/microliter for patients with documented benign ethnic neutropenia (BEN).The monitoring schedule is every week for the first 6 months, every 2 weeks for the following 6 months, and monthly indefinitely thereafter if ANC remains at least 1500/microliter (at least 1000/microliter for BEN). If ANC <1500/microliter (<1000/microliter for BEN), the monitoring frequency and the clinical decision regarding the use of clozapine will be adjusted accordingly based on the actual ANC level following the established guideline.[65]
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