PHARMACOLOGICAL OPTIONS

FOR
TREATMENT-RESISTANT
SCHIZOPHRENIA(TRS)

DR.MD.SELIM BABU
PHASE-B RESIDENT
DEPARTMENT OF PSYCHIATRY
BSMMU
DEFINITION

• Treatment-resistant schizophrenia defined as a failure to respond to two trial

of anti-psychotic medications,one being second generation,of adeqauet dose
and duration.
TREATMENT OPTIONS FOR TRS

• Clozapine
Clozapine monotherapy
Augmentation of Clozapine
• Aternatives to clozapine
ATERNATIVES TO CLOZAPINE
• Non-clozapine antipsychotics monotherapy in high doses
• Non-clozapine antipsychotics polypharmacy
• Adjuncts to antipsychotics
Anti-inflammatory agents
NMDA receptor modulators
Antidepressants
Antiseizure medications
• Physical treatments
• Psychological therapies
SUMMARY OF CLOZAPINE TREATMENT
• The choice of treatment for people with TRS
• Response rate 30-75%
• Can be initiated within 6-12 months of treatment resistance.
• Response usually seen in the range 150–900mg/day
• Plasma levels range 350–420μg/l.
• A plasma level of 350μg/l should be aimed to ensure an adequate trial, but
response may occur at lower plasma level.
SUMMARY OF CLOZAPINE TREATMENT

• Started at a dose of 12.5mg at night

• On day 2, dose can be increased to 12.5mg twice daily.
• Then dose can be increased by 25–50mg/day, until a dose of 300mg a day is
achieved in 2–3 weeks.
• Further dosage increases slowly 50–100mg /week.
SUMMARY OF CLOZAPINE TREATMENT

• The total clozapine dose should be divided (usually twice daily)

• Dose gradually tapered over 1-2 weeks.
• If therapy is interrupted for >48 hrs, must be started at
12.5-25 mg /day
• Should be continue for at least 6 months for an adequate trial.
• Initial laboratory work-up,dose titration,monitoring of blood and
screening for other side effects must be ensured.
AUGMENTATION OF CLOZAPINE

• Should be considered after at least 3 months of optimized clozapine

momotherapy.
• An agent should be chosen considerning its complementay receptor profile
to clozapine and resultant burden of side-effects.
OPTIONS FOR AUGMENTING CLOZAPINE
• Amisulpride (400–800mg/day)
• Aripiprazole (15–30mg/day)
• Haloperidol (2–3mg/day)
• Risperidone (2–6mg/day)
• Sulpiride (400mg/day)
• Topiramate (50–300mg/day)
• Sodium valproate (400–800mg/day)
• Lamotrigine (25–300mg/day)
• Omega-3 triglycerides (2–3g EPA daily)
ATERNATIVES TO CLOZAPINE
ATERNATIVES TO CLOZAPINE
ATERNATIVES TO CLOZAPINE
REFERENCE

• The Maudsley Prescribing Guidelines in Psychiatry

• BAP Guidelines for Management of Schizophrenia
Thank You