Bupropion and Amantadine in Schizophrenia
Bupropion (Wellbutrin)
Bupropion can be safely and effectively used in patients with schizophrenia for depression and negative symptoms when combined with stable antipsychotic medication, with negligible risk of inducing psychosis under these conditions. 1
Evidence for Safety and Efficacy
229 schizophrenic patients on stable antipsychotic regimens were successfully treated with bupropion and experienced marked clinical improvement without developing psychosis, demonstrating robust safety when antipsychotics are maintained 1
All patients in a consecutive case series (N=5) experienced significant improvements in major depressive episodes when bupropion extended release was added to stable antipsychotic doses 2
Psychotic positive symptoms remained stably absent during bupropion treatment, while both negative symptoms and global psychopathology considerably improved 2
The risk of bupropion-induced psychosis is negligible in schizophrenic patients treated with concomitant antipsychotics, as 93% of reported psychotic episodes (28 of 30 cases) occurred without antipsychotic coverage 1
Clinical Application
Bupropion is particularly valuable for treating negative symptoms including anhedonia, amotivation, alogia, affective flattening, and passive social withdrawal that persist after positive symptom control 3
The extended-release formulation is preferred, as 57% of bupropion-induced psychoses were associated with immediate-release formulations 1
Critical requirement: Patients must be on stable antipsychotic medication before initiating bupropion 2, 1
Monitoring Considerations
EEG monitoring should be provided, as subtle electroencephalographic deteriorations have been observed even without clinical seizures 2
Electroencephalographic abnormalities occur frequently with bupropion treatment in this population 1
Pharmacokinetic interactions with antipsychotics are rare 1
Amantadine
Amantadine should be used with extreme caution in schizophrenic patients due to high risk of serious CNS toxicity, including hallucinations, delirium, agitation, and seizures, particularly in those with psychiatric disorders. 4
Critical Safety Concerns
Serious CNS side effects (marked behavioral changes, delirium, hallucinations, agitation, seizures) are associated with high plasma drug concentrations and occur most often among persons with psychiatric disorders 4
A documented case of generalized convulsion with multiple spikes on EEG occurred in a 63-year-old schizophrenic patient when amantadine was increased from 200 mg to 300 mg daily 5
The EEG normalized and seizures ceased immediately after amantadine discontinuation 5
Dosing Restrictions for Psychiatric Patients
The maximum daily dose must not exceed 200 mg, and lower doses are strongly recommended for patients with psychiatric disorders 4
Dose reduction significantly reduces the incidence and severity of serious side effects in high-risk populations including those with psychiatric disorders 4, 6
Patients with seizure disorders or psychiatric disorders require particularly close observation and lower dosing 4, 6
Risk-Benefit Assessment
While amantadine is used for extrapyramidal symptoms, the risk of inducing psychotic symptoms, seizures, and behavioral changes in schizophrenic patients is substantial 4, 5
The epileptic mechanisms may be related to dopamine's modulating role in the CNS, which is already dysregulated in schizophrenia 5
If amantadine must be used in schizophrenic patients, start at the lowest possible dose (≤100 mg/day), monitor closely for CNS toxicity, and discontinue immediately if behavioral changes or psychotic symptoms emerge 4, 6