Schizophrenia: Drug Therapy

Therapy goals

• Prevention of schizophrenic episodes or relapse prophylaxis (measures to avert recurrence of a disorder.
• “Recovery” (restoration of functional capacity for a self-determined life).

Therapy recommendations

General advice

• Because there are only small differences in the effects of the various antipsychotics, particular attention should be paid to side-effect-guided antipsychotic pharmacotherapy for acute treatment with a “number needed to treat” (NNT) of 5 to 8.
• A combination of drug therapy with psychotherapy and psychosocial training is always indicated (see below “Further therapy”).
• Drug therapy should be started as early as possible to improve the prognosis.
• Antipsychotic monotherapy is generally preferred due tobetter controllability, reduced risk of side effects and interactions (exception: therapy resistance: see below).
• Currently available antipsychotics act by blocking dopamine receptors.
• For general consideration:
  • High-potency antipsychotics have a strong antipsychotic but low sedative (calming) effect and often cause extrapyramidal motor side effects
  • Low-potency antipsychotics have a low antipsychotic effect, strongly sedating, are often cardiotoxic (“heart-damaging”) and rarely cause extrapyramidal-motor side effects
• In the case of pharmacological resistance to therapy, pseudotherapy resistance (see “Further notes” below) must be excluded.
• For all agents, regular blood count, blood pressure, and ECG examinations must be performed.

Special recommendations

• According to the current AWMF S3 guideline, antipsychotic monotherapy is generally preferred in the treatment of schizophrenia.
• Acute therapy: e.g., aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone (atypical antipsychotics); haloperidol, perphenazine, thioridazine (conventional antipsychotics); dosage depending on 1st or 2nd episode, respectively.
  • In case of therapy resistance, clozapine should be used; check the presence of the indication already after 2, at the latest 4 weeks!
  • Only if three monotherapies including clozapine were unsuccessful, the guideline agrees to a combination therapy.
  • Maintenance therapy for multiple episodes: Aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone (atypical antipsychotics); fluphenazine, fluphenazine decanoate, flupentixol, flupentixol decanoate, haloperidol, haloperidol decanoate, perazinenantate, perphenazine, perphenazine decanoate (conventional antipsychotics); clozapine (for treatment resistance).
    • Duration of therapy: therapy should be continued for >1 year; therapy should be phased out.
• Continuous antipsychotic relapse prophylaxis is required (NNT: 3).
  • Duration of therapy: duration of therapy depending on factors such as severity of in index episode, stability of social network, and comorbidities (concomitant disorders)
• Special treatment conditions:
  • Catatonia (syndrome with symptoms including: Stupor (rigidity of the whole body), bizarre postural stereotypies, catalepsy (retention of body position after passive movement), and mutism (patients do not speak) while awake) is treated primarily with lorazepam.
  • Depression and suicidality*
  • Post-traumatic stress disorder (PTSD)* .
  • Substance use disorders (alcohol* , tobacco* , cannabis* ).
• See also under “Further therapy”.

* See under the diseases / substances with the same name.

Further notes

• Clozapine
  • Note [guidelines: S3 guideline]:
    • Pseudotherapy resistance should be excluded before initiating therapy with clozapine.
    • In the case of pharmacologic therapy resistance, after pseudotherapy resistance has been ruled out, the following questions must be asked:
      • Is there a diagnosis of schizophrenia?
      • Are there adequate serum levels of the antipsychotics (non-adherence; fast-metabolizing).
      • Is there sufficient duration of therapy?
      • Is there substance use (e.g., amphetamines, cannabis)?
  • Therapy-resistant schizophrenia is treated with clozapine; regular leukocyte checks determination (examination of white blood cells) due toagranulocytosis risk (severe reduction of granulocytes, a subgroup of leukocytes) required!
  • Use clozapine if therapy is resistant: Recurrence rates in patients with schizophrenia were most significantly reduced with clozapine and long-acting injectable antipsychotics.
  • Fewer deaths and self-inflicted injuries (eg, cutting, poisoning, suicide attempts) with clozapine than with other antipsychotic therapies.
  • A low baseline SOFAS (Social and Occupational Functioning Assessment Scale) score is the most reliable predictor (“predictive value”) of improvements in SOFAS after 6 and 12 weeks of clozapine therapy
• Antipsychotics – efficacy according to meta-analysis: most effective with respect to the primary end point were clozapine, amisulpride, zotepine, olanazapine, and risperidone.
  • Dose-response relationship of antipsychotics and the equivalent doses: mean doses at which 50% (ED50) or 95% (ED95) of the maximum effect was achieved see below.
• Note: One of the major problems in the treatment of patients suffering from schizophrenia is poor compliance; approximately 50% of patients discontinue drug therapy within a short period of time during the first episode.

Other therapeutic options

• Antidepressants can be used for concomitant depression.The prevalence (illness frequency) of depressive symptomatology is 25% in persons suffering from schizophrenia. The effectiveness of additional medication with antidepressants in antipsychotic treatment is given.
• Benzodiazepines are considered to have a positive effect on schizophrenia (especially lorazepam in catatonia).
• Cariprazine: for acute schizophrenic symptoms, cariprazine is about as effective as aripirazole, asenapine, lurasidone, and ziprasidone, but less effective than olanzapine,quetiapine, and risperidone
• In women of childbearing age, adjunctive treatment with transdermal estradiol (estrogen patch) in addition to usual antipsychotic therapy can significantly alleviate positive symptoms such as delusions, hallucinations, and impaired thinking; older patients (38 to 42 years of age) benefited particularly from estrogen adjunctive treatment.