What are the side effects of loxapine?

Side Effects of Loxapine

Loxapine causes frequent extrapyramidal symptoms (tremor, rigidity, akathisia) and sedation, with a side effect profile similar to typical antipsychotics, including risks of tardive dyskinesia, neuroleptic malignant syndrome, and cardiovascular effects. 1

Neurological and Movement Disorders

Extrapyramidal Symptoms (EPS)

• Parkinsonian symptoms occur frequently, particularly during the first few days of treatment, manifesting as tremor, rigidity, excessive salivation, and masked facies 1
• Akathisia (motor restlessness) is reported relatively frequently and can be controlled by dose reduction or antiparkinson medications 1
• Acute dystonia may develop in susceptible individuals during initial treatment days, presenting as prolonged muscle contractions, neck spasms progressing to throat tightness, swallowing difficulty, breathing problems, and tongue protrusion 1
• Males and younger patients face elevated risk for acute dystonic reactions 1
• Loxapine causes a high incidence of extrapyramidal reactions comparable to phenothiazines and butyrophenones 2
• When compared to atypical antipsychotics, loxapine produces significantly more extrapyramidal adverse effects (RR 2.18,95% CI 1.6-3.1) 3

Tardive Dyskinesia

• Persistent tardive dyskinesia may appear during long-term therapy or after discontinuation, with greater risk in elderly patients on high-dose therapy, especially females 1
• The syndrome manifests as rhythmical involuntary movements of tongue, face, mouth, or jaw (tongue protrusion, cheek puffing, mouth puckering, chewing movements), sometimes accompanied by extremity movements 1
• No known effective treatment exists for tardive dyskinesia; antiparkinson agents do not alleviate symptoms 1
• Fine vermicular tongue movements may signal early syndrome development 1

Neuroleptic Malignant Syndrome (NMS)

• NMS has been reported with loxapine, presenting as altered mental status, hyperthermia, severe rigidity, and autonomic instability 1
• Risk factors include dehydration, physical exhaustion, preexisting brain disease, and concomitant psychotropic medications 4

Cardiovascular Effects

• Tachycardia, hypotension, hypertension, orthostatic hypotension, lightheadedness, and syncope have been reported 1
• Rare cases of ECG changes similar to phenothiazines have occurred, though causality with loxapine remains uncertain 1
• Tachycardia occurs frequently, especially during early treatment stages 2

Sedation and Cognitive Effects

• Sedation occurs frequently, particularly during early treatment stages 2, 3
• Drowsiness is a chief side effect, especially in elderly patients 5

Anticholinergic Effects

• Dry mouth, nasal congestion, constipation, blurred vision, urinary retention, and paralytic ileus have been reported 1
• These anticholinergic effects occur less commonly than EPS but follow patterns seen with older antipsychotics 2

Hematologic Effects

• Rarely, agranulocytosis, thrombocytopenia, and leukopenia may occur 1

Dermatologic Effects

• Dermatitis, facial edema (puffiness), pruritus, rash, alopecia, and seborrhea have been documented 1

Gastrointestinal and Hepatic Effects

• Nausea and vomiting occur in some patients 1
• Hepatocellular injury with SGOT/SGPT elevation has been reported, and rarely jaundice and/or hepatitis questionably related to loxapine 1

Endocrine and Metabolic Effects

• Weight gain or weight loss may occur 1
• Rarely, galactorrhea, amenorrhea, gynecomastia, and menstrual irregularities of uncertain etiology have been reported 1

Other Effects

• Dyspnea, ptosis, hyperpyrexia, flushed facies, headache, paresthesia, and polydipsia have been documented 1
• Precipitation of epileptic seizures can occur, similar to older antipsychotic drugs 2
• Slight increase in blood pressure has been observed in elderly patients 5

Dosing Considerations for Side Effect Management

• Most extrapyramidal symptoms are not severe and can be controlled by dose reduction or administration of antiparkinson drugs 1
• In elderly patients, therapeutic dosage range is 10-80 mg daily—approximately half that used for younger patients—which may reduce side effect burden 5

Comparative Side Effect Profile

• Loxapine's adverse effect profile is similar to typical antipsychotics rather than atypicals 3, 6
• At high doses for chronic treatment, loxapine demonstrates an adverse effects profile comparable to typical antipsychotics 6