What are the side effects of loxapine (an antipsychotic medication)?

Side Effects of Loxapine

Loxapine causes frequent extrapyramidal symptoms (EPS) similar to typical antipsychotics, with parkinsonian symptoms, akathisia, and acute dystonia being the most common adverse effects, particularly during the first few days of treatment. 1

Neurological Side Effects

Extrapyramidal Symptoms (Most Common)

• Parkinsonian symptoms occur frequently and include tremor, rigidity, excessive salivation, and masked facies, typically appearing within the first few days of treatment 1
• Akathisia (motor restlessness) is reported relatively frequently and manifests as an inability to sit still, pacing, or physical agitation 1
• Acute dystonia can occur in susceptible individuals during the first few days, presenting as spasm of neck muscles, tightness of throat, swallowing difficulty, difficulty breathing, and/or tongue protrusion 1
• Young males are at elevated risk for acute dystonic reactions 1
• These symptoms are usually not severe and can be controlled by reducing loxapine dosage or administering antiparkinson drugs 1

Tardive Dyskinesia

• Tardive dyskinesia may appear with long-term therapy or after drug discontinuation, characterized by rhythmical involuntary movements of the tongue, face, mouth, or jaw 1
• The risk is greater in elderly patients on high-dose therapy, especially females 1
• The symptoms are persistent and in some patients appear to be irreversible 1
• There is no known effective treatment for tardive dyskinesia; antiparkinson agents do not alleviate these symptoms 1
• Fine vermicular movements of the tongue may be an early sign, and stopping medication at that time may prevent syndrome development 1

Neuroleptic Malignant Syndrome (NMS)

• NMS is a potentially fatal symptom complex that has been reported with loxapine 1
• Clinical manifestations include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias) 1
• Management requires immediate discontinuation of loxapine, intensive symptomatic treatment, and medical monitoring 1

Other Neurological Effects

• Sedation occurs frequently, especially during early stages of treatment 1, 2
• Dizziness, faintness, staggering gait, shuffling gait, muscle twitching, and weakness have been reported 1
• Insomnia, agitation, tension, seizures, akinesia, slurred speech, numbness, and confusional states can occur 1

Cardiovascular Effects

• Tachycardia, hypotension, hypertension, orthostatic hypotension, lightheadedness, and syncope have been reported 1
• ECG changes similar to those seen with phenothiazines have been reported in a few cases 1
• Loxapine may cause postural hypotension and motor instability, which may lead to falls and consequently fractures or other injuries 1

Anticholinergic Effects

• Dry mouth, nasal congestion, constipation, blurred vision, urinary retention, and paralytic ileus have occurred 1
• These effects are less common than with low-potency typical antipsychotics 3

Hematologic Effects

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

Gastrointestinal and Hepatic Effects

• Nausea and vomiting have been reported in some patients 1
• Hepatocellular injury (SGOT/SGPT elevation) has been reported in association with loxapine 1
• Rarely, jaundice and/or hepatitis questionably related to loxapine treatment 1

Dermatologic Effects

• Dermatitis, edema (puffiness of face), pruritus, rash, alopecia, and seborrhea have been reported 1

Endocrine and Metabolic Effects

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

Other Adverse Effects

• Dyspnea, ptosis, hyperpyrexia, flushed facies, headache, paresthesia, and polydipsia have been reported 1
• Dysgeusia (taste disturbance) is common with inhaled loxapine formulations 4

Clinical Context and Comparative Profile

Loxapine is classified as having an "in-between" side effect profile among typical antipsychotics, positioned between high-potency agents (like haloperidol) and low-potency agents (like chlorpromazine) 3. Research confirms that loxapine causes a high incidence of extrapyramidal reactions similar to phenothiazines and butyrophenones 2. When compared to atypical antipsychotics, loxapine causes significantly more extrapyramidal adverse effects (RR 2.18,95% CI 1.6-3.1) 5.

Important Clinical Caveats

• Loxapine may impair mental and/or physical abilities, especially during the first few days of therapy, requiring caution with activities requiring alertness 1
• Complete fall risk assessments should be performed when initiating treatment and recurrently for patients on long-term therapy 1
• The smallest dose and shortest duration of treatment producing a satisfactory clinical response should be sought 1
• If signs of tardive dyskinesia appear, drug discontinuation should be considered, though some patients may require continued treatment despite the syndrome 1
• In elderly patients, therapeutic dosage range is approximately half that used for younger patients (10-80 mg daily vs. higher doses in younger adults) 6