Benzodiazepines in combination with antipsychotic drugs for schizophrenia: GABA-ergic targeted therapy

Antipsychotics are a key intervention strategy in pharmacotherapy of schizophrenia. However, benzodiazepines are often prescribed to control sleep disturbances, anxiety or behavioural disinhibition. There is clinical evidence for the beneficial effect of the combined treatment of antipsychotics and benzodiazepines resulting in more favorable treatment outcome in schizophrenia with regard to positive and negative symptoms. This clinical phenomenon seems to be associated with the GABA-ergic activit ythat is believed to be disrupted in the schizophrenia and direct benzodiazepines effect on GABA-A receptors. In the brain there are both excitatory and inhibitory neurotransmitters which cooperate between themselves maintaining the proper functioning of the brain. GABA neurons carry inhibitory signals that help keep brain activity at optimal levels of operation, Glutamate, on the other hand, carry excitatory signals. As the interplay between these two exists they keep the dopamine levels in the average levels. The disruption of GABA-ergic transmission in schizophrenia may induce alternations in dopaminergic neurotransmission providing no inhibitory effect to the central glutamate activity, resulting in the rise of the dopamine levels being associated with psychosis precipitation. Benzodiazepines are believed to reduce presynaptic dopamine release at the mesolimbic level and delay postsynaptic adaptation of dopaminergic neurons to antipsychotics potentiating the action of antipsychotics in resistant schizophrenia. Benzodiazepines also act on mesocortical regions where antipsychotics are less effective and where there is a particular sensitivity to stress. This association is particularly useful in resistant patients or in patients with severe anxiety with or without intolerance to antipsychotics. Improvement concerns anxious symptoms but also positive symptoms (hallucinations, delirium and dissociative syndrome) and negative (social withdrawal, affect flattening). As the available studies are limited there is some clinical evidence that the use of antipsychotic drugs with addition of benzodiazepines can provide better general outcome in ill patients than antipsychotics administration alone.