The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.

The discovery of the antipsychotic properties of chlorpromazine in the 1950s was a fundamental event for the practice of psychiatry and for the genesis of the so-called "psychopharmacological revolution."

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade’s experiments with lithium and the beginning of the so-called “Psychopharmacological Revolution” in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

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Objective: This study aimed to compare the efficacy of long-acting risperidone and zuclopenthixol in subjects with schizophrenia and substance abuse. Method:A total of 115 subjects with schizophrenia and substance use disorders were enrolled for an open, randomized, controlled, 6-month follow-up study. Fifty-seven subjects were selected for treatment with long-acting injectable risperidone, while another 58 were treated with zuclopenthixol-depot.Results: Long-acting risperidone patients presented fewer positive urine tests (8.67 compared with 10.36, P = 0.005), showed improved scores on the Positive and Negative Syndrome Scale, and showed better compliance with the Substance Abuse Management program. The use of long-acting risperidone and less severe dependence explained the outcome at the end of the follow-up.Conclusions: Long-acting injectable risperidone was more effective than zuclopenthixol-depot in improving substance abuse and schizophrenia symptoms in subjects with dual diagnosis. (Can J Psychiatry 2006;51:531-539) Information on funding and support and author affiliations appears at the end of the article. Clinical Implications· Long-acting risperidone is more effective than zuclopenthixol-depot in improving substance abuse in subjects with schizophrenia. · Long-acting risperidone improves the efficacy of a cognitive-behavioural program for managing substance abuse. · Atypical antipsychotics could be the best pharmacologic strategy in the treatment of subjects with schizophrenia and substance abuse comorbidity. Limitations· The study had an open design. · Results may not be generalizable to other clinical populations. · We included subjects with family support.

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