Abstract
Atypical antipsychotic drugs were introduced in the early 1990s. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics are effective against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic but also in affective disorders, on their own or as adjuncts to antidepressant drugs. This review presents the neural mechanisms of currently existing atypical antipsychotics and putative antipsychotics currently being investigated in preclinical and clinical studies and how these relate to their effectiveness in mood disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Typical antipsychotics act almost exclusively on the dopamine system. Atypical drugs, however, modulate serotonin (5-HT), norepinephrine, and/or histamine neurotransmission as well. This multimodal mechanism of action putatively underlies the beneficial effect of atypical antipsychotics in mood and anxiety disorders. Interestingly, novel experimental drugs having dual antipsychotic and antidepressant therapeutic potential, such as histamine, adenosine, and trace amine-associated receptors (TAAR) ligand, are also characterized by a multimodal stimulatory effect on central 5-HT, norepinephrine, and/or histamine transmission. The multimodal stimulatory effect on central monoamine neurotransmission may be thus primarily responsible for the combined antidepressant and antipsychotic therapeutic potential of certain central nervous system (CNS) drugs.
Highlights
The first antipsychotic drug, chlorpromazine, a member of the phenothiazine family, was discovered serendipitously in 1951
Phenothiazines were the first drugs shown to be effective in easing the positive symptoms of schizophrenia; they were, less effective against negative and cognitive symptoms and had multiple adverse side effects
The number of of neurons recorded in each group is provided within the histograms. ** p < 0.01 and *** p < 0.001 neurons recorded in each group is provided within the histograms. ** p < 0.01 and *** p < 0.001 in in comparison with control animals
Summary
The first antipsychotic drug, chlorpromazine, a member of the phenothiazine family, was discovered serendipitously in 1951. Phenothiazines were the first drugs shown to be effective in easing the positive symptoms of schizophrenia; they were, less effective against negative and cognitive symptoms and had multiple adverse side effects Later, butyrophenones, another group of typical antipsychotic drugs, were discovered, with the best known being haloperidol. Atypical antipsychotic drugs as a monotherapy are effective in bipolar, not unipolar. Atypical antipsychotic drugs as a monotherapy are effective in bipolar, not unipolar depression [9,10,11]. Clinical effectiveness as monotherapy in bipolar disorder has been shown for aripiprazole [12,13], asenapine [14], olanzapine, quetiapine [15], and risperidone [16].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
