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Article

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

Department of Pharmacology and Human Physiology, University of Bari Medical School, Bari, Italy (L.G.C.); Department of Pharmacological Sciences, University of Palermo, Palermo, Italy (L.S.); Department of Pharmacology and Physiology, University of Roma "La Sapienza," Rome, Italy (V.C.)

Abstract

I. Introduction

II. Neurotransmitters and Brain Development

A. Dopaminergic System

B. Serotonergic System

C. Noradrenergic System

D. GABAergic System

III. Antipsychotics and Antiepileptics

A. Antipsychotic Drugs

1. Typical Antipsychotics.

2. Atypical Antipsychotics.

B. Antiepileptic Drugs

1. Valproic Acid.

2. Phenytoin.

3. Phenobarbital.

4. Carbamazepine.

5. ''New'' Antiepileptics.

IV. Anxiolytics and Mood Stabilizers

A. Benzodiazepines

B. Lithium

V. Antidepressants

A. Tricyclic and Atypical Antidepressants

B. Monoamine Oxidase Inhibitors

C. Selective Serotonin Reuptake Inhibitors

D. Novel Antidepressants

VI. Neuroactive Herbal Drugs

A. St. John's Wort

B. Ginkgo Biloba

C. Kava

D. Valerian

VII. Future Prospects and Research Needs

The advent of psychotherapeutic drugs has enabled management of mental illness and other neurological problems such as epilepsy in the general population, without requiring hospitalization. The success of these drugs in controlling symptoms has led to their widespread use in the vulnerable population of pregnant women as well, where the potential embryotoxicity of the drugs has to be weighed against the potential problems of the maternal neurological state. This review focuses on the developmental toxicity and neurotoxicity of five broad categories of widely available psychotherapeutic drugs: the neuroleptics, the antiepileptics, the antidepressants, the anxiolytics and mood stabilizers, and a newly emerging class of nonprescription drugs, the herbal remedies. A brief review of nervous system development during gestation and following parturition in mammals is provided, with a description of the development of neurochemical pathways that may be involved in the action of the psychotherapeutic agents. A thorough discussion of animal research and human clinical studies is used to determine the risk associated with the use of each drug category. The potential risks to the fetus, as demonstrated in well described neurotoxicity studies in animals, are contrasted with the often negative findings in the still limited human studies. The potential risk for the human fetus in the continued use of these chemicals without more adequate research is also addressed. The direction of future research using psychotherapeutic drugs should more closely parallel the methodology developed in the animal laboratories, especially since these models have already been used extremely successfully in specific instances in the investigation of neurotoxic agents.

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