CINP Schizophrenia Guidelines

The schizophrenia treatment algorithm for the CINP website produced by Stefan Leucht, Celso Arango, Shitij Kapur, Wolfgang Fleischhacker, Jim van Os, Scott Stroup and Christoph Correll is now available.

The structure is as follows: we have a number of recommendations which are broadly classified in “A) Treatment of an acute episode”, “B) Specific patient populations/symptoms”, “C) maintenance treatment” and “D) prophylaxis/management of side-effects”. Each recommendation is backed-up by a short paragraph summarising the evidence. The order of the recommendations partly follows the natural flow of treatment. And there are two tables (one with doses, the other one with side-effects) which are quoted several times.


Grades of recommendations

A) Systematic review of randomized controlled trials or single randomized controlled trials
B) Systematic review of case control or cohort studies, or single case control or cohort studies
C) Case series, case reports, expert opinion, good clinical practice

We indicated with minus (-) signs whether despite available evidence we considered a given evidence level as borderline. The recommendations are in part based on a previous publication (Leucht et al., 2011), which has been updated and amended, but other passages remained unchanged.

A) Treatment Of An Acute Episode Of Schizophrenia B) Specific patient populations/symptoms C) Relapse Prevention With Antipsychotic Drugs D) Prophylaxis/Management Of Side-Effects References
Adverse EffectMechanismDose/AMIARIASECLOILOLUROLAPALIQUERISSERZIP CPZHALPER
Titration
Dependent
Anticholinergic M1-4 blockade++000+++ 00++ 0+/++ 000++ 00/+
Acute Parkinsonism D2 blockade++++ + ++ 00/++ /++0/+ ++ 0++ 0/++ + +++ ++
Akathisia?D2 blockade and, alpha, 5HT interaction+++++++++0/++/+++ +++++/++ + +++ ++
Cerebrovascular events*?D2 mediated hyper-coagulability0 ?+? ++? +? +? +? ++? ++ +? +? +? +? +?
DiabetesWeight gain, ?direct effects0 ?0/+ 0/+ 0/+++++ 0/+ ++++ ++++0/+ +++0/+ +
↑ LipidsWeight gain, ?direct effects0/++ 0/+ 0/+++++ 0/+ ++++ ++++0/+ +++0/+ +
Hypersalivation (due to overproduction)M4 agonism+000++00000000000
Neutropenia?+?0/+0/+0/+++0/+0/+0/+0/+0/+0/+0/+0/+0/+0/+0/+
OrthostasisAlpha 1 blockade+++ 0/+0/++++++++0/++++++ b++0++0+
↑ Prolactin/ sexual dysfunctionD2 blockade++++++0+ 00/+ + ++++ 0+++ ++ + ++ /+++++
↓ ProlactinD2 agonism+ ?0+0000000000000
↑ QTc intervalCardiac ion channel effects+++0/+ + + ++ 0/+0/+ + + + ++/+++++0/+ 0++
SedationH1 blockade+++ 0/+0/+++++0/+ +/+++/++0/+++ b+0/++++++
Seizures? dopamine blockade+++0/+0/+0/+++ 0/+0/+0/+0/+0/+0/+0/+0/+0/+0/+0/+
Tardive Dyskinesia? D2 receptor desensitization++0/+ 0/+ 0/+00/+ 0/+ 0/+0/+ 0/+0/+0/+0/+ ++++ ++
Withdrawal DyskinesiaD2 blockade rebound+++ ++/+++0++0/++0/++0/++0/++++/++
Weight Gain a?H1, D2, 5HT2c blockade+0/+0/++++++/++0/++++++++++++0/+++++++

Table 1: Side-effect profiles of selected antipsychotic drugs

AMI=amisulpride; ARI= aripiprazole; ASE= asenapine; CLO= clozapine; ILO= iloperidone; LUR=lurasidone; OLA =olanzapine; PALI= paliperidone; QUE= quetiapine; RIS= risperidone; SER=sertindole; ZIP= ziprasidone; CPZ= chlorpromazine; HAL= haloperidol; MOL= molindone; PER= perphenazine

a Extent/risk depends on degree of prior weight gain on psychotropic medications, weight gain potential of specific medication and patient susceptibility, b risk of quetiapine extended release may be low than that of quetiapine immediate release. Modified and extended from (Schimmelmann et al., 2013), *evidence derived only from studies in elderly patients with dementia, data were available only for olanzapine, quetiapine, risperidone and aripiprazole, but all medications have received a class label by the FDA.

Reference:

Schimmelmann, B.G., Schmidt, S.J., Carbon, M., Correll, C.U., 2013. Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach. Current opinion in psychiatry 26, 219-230.

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