Treatment-resistant schizophrenia

Active Ingredient: Clozapine

Indication for Clozapine

Population group: only adults (18 years old or older)

Clozapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics.

Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration.

For this indication, competent medicine agencies globally authorize below treatments:

12.5-900 mg in 2 divided doses daily

Route of admnistration


Defined daily dose

12.5 - 900 mg

Dosage regimen

From 6.25 To 450 mg 2 time(s) per day every day

Loading dose

12.5 mg

Detailed description

Starting therapy

12.5 mg once or twice on the first day, followed by 25 mg once or twice on the second day. If well tolerated, the daily dose may then be increased slowly in increments of 25 to 50 mg in order to achieve a dose level of up to 300 mg/day within 2 to 3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50 to 100 mg at half-weekly or, preferably, weekly intervals.

Therapeutic dose range

In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. The total daily dose may be divided unevenly, with the larger portion at bedtime.

Maximum dose

To obtain full therapeutic benefit, a few patients may require larger doses, in which case judicious increments (not exceeding 100 mg) are permissible up to 900 mg/day. However, the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.

Maintenance dose

After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses. Careful downward titration is therefore recommended. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, once daily administration in the evening may be appropriate.

Ending therapy

In the event of planned termination of clozapine therapy, a gradual reduction in dose over a 1- to 2-week period is recommended. If abrupt discontinuation is necessary, the patient should be carefully observed for the occurrence of withdrawal reactions.

Re-starting therapy

In patients in whom the interval since the last dose of clozapine exceeds 2 days, treatment should be re-initiated with 12.5 mg given once or twice on the first day. If this dose is well tolerated, it may be feasible to titrate the dose to the therapeutic level more quickly than is recommended for initial treatment. However, in any patient who has previously experienced respiratory or cardiac arrest with initial dosing, but was then able to be successfully titrated to a therapeutic dose, re-titration should be carried out with extreme caution.

Active ingredient


Clozapine has been shown to be an antipsychotic agent that is different from classic antipsychotics. Clozapine has potent anti-alpha-adrenergic, anticholinergic, antihistaminic, and arousal-reaction-inhibiting effects. It has also been shown to possess antiserotoninergic properties.

Read more about Clozapine

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