Nonselective serotonin reuptake inhibitors

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

Fourth, as an expert in criminal and civil cases, I have studied the lives of many individuals who—under the influence of psychoactive drugs such as SSRIs, nonselective serotonin reuptake inhibitors (NSRIs), and benzodiazepines—have committed acts of aggression that were wholly alien to their character and antithetical to their prior behavior. It is, of course, well known that the illegal use of stimulant drugs, such as meth-amphetamine and cocaine, can be associated with paranoid reactions and violence. 

NSRI Antidepressants. Nonselective serotonin reuptake inhibitors (NSRI)also block the reuptake of norepinephrine. Several of the old tricyclic antidepressants belong in this category. Imipramine and desipramine reduce REM sleep because of the increased norepinephrine levels at postsynaptic receptors caused by reduced reuptake of norepinephrine. 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Figure 7.3. Structural formulae of the noradrenaline (norepinephrine)/dopamine reuptake inhibitor amfebutamone (bupropion) and some nonselective noradrenaline and serotonin (5-hydroxytr3 tamine 5-HT) reuptake inhibitors (venlafaxine, and...

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