Selective serotonin reuptake inhibitors. See

Fluvoxamine, an antidepressant, is a potent and selective serotonin reuptake inhibitor (see Figure 86) which is devoid of anticholinergic, antihistaminic, or cardiotoxic properties. Fluvoxamine offers depressed patients an equivalent level of therapeutic benefit when compared with imipramine (see Tables 5 through 7). 

Reuptake of serotonin by enteric neurons and epithelium is mediated by the same mechanism as 5-HT reuptake by serotonergic neurons in the CNS. This reuptake therefore also is blocked by selective serotonin reuptake inhibitors (see Chapter 17), which explains the common side effect of diarrhea that accompanies the use of these agents. 

Toxicity Adverse effects include insomnia, mood changes, dyskinesias, gastrointestinal distress, and hypotension. Meperidine in combination with selegiline has caused agitation, delirium, and death. Selegiline has been implicated in the serotonin syndrome when used in patients taking selective serotonin reuptake inhibitors (see Chapter 30). 

In many clinical trials a positive control of a clinically established drug is often used for comparison purposes for example, a novel selective serotonin reuptake inhibitor (SSRI), may be compared with a more established tricyclic antidepressant, such as imipramine. The aim is to see whether the new SSRI is more efficacious or has fewer adverse side effects than the more established tricyclic (Chapter 12). In many such comparisons the new and older treatments are equally efficacious at relieving depression, but the newer drugs display fewer side effects this means that they are better tolerated by patients, so that they are more willing to continue taking the tablets. The high rates of compliance also mean that, in overall terms, newer drugs with fewer side effects tend to be more efficacious. 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

Sertraline is a recent antidepressant that is called a selective serotonin reuptake inhibitor (SSRI). It is chemically unrelated to the older tricyclic antidepressants (see Section 5.3). It works by preventing the movement of the neurohormone serotonin into nerve endings. It can help to improve mood and mental alertness, increase physical activity, and improve sleep patterns. It is prescribed for obsessive-compulsive disorder and obesity. It may offer some advantage over fluoxetine by exhibiting little central nervous system (CNS) action. It has less sedation and anxiety and is shorter acting. 

A life-threatening condition, when selective serotonin reuptake inhibitors (SSRIs) and 5-hydroxytryptamine receptor agonists (triptans) are used together. However, many other drugs have been implicated (see below). Signs and symptoms of serotonin syndrome include the following ... 

Antidepressant drugs, such as the tricyclic antidepressants and the selective serotonin reuptake inhibitors (SSRIs), are very important for the treatment of psychotic depression (see Chapter 34). They have been shown to be effective when used in the treatment of several anxiety disorders, including general anxiety, obsessive-compulsive disorder, and several phobias, including agoraphobia. Because the SSRIs are less toxic than the tricyclic antidepressants, their use in the treatment of anxiety is safer and less likely to produce serious side effects. 

It is of note that Hypericum, often described as the natural Prozac, has the opposite effect of fluoxetine— and selective serotonin reuptake inhibitors (SSRIs) in general—on the CYP system. Fluoxetine inhibits several CYP isoenzymes, potentially resulting in increased blood levels of drugs metabolized through this pathway (See Chapter 22). 

Selective serotonin reuptake inhibitors. Currently available selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. At present, expert opinion does not support the usefulness of these serotonergic compounds in the treatment of core ADHD symptoms (National Institute of Mental Health, 1996). Nevertheless, because of the high rates of comorbidity in ADHD, these compounds are frequently combined with effective anti-ADHD agents (see Combined Pharmacotherapy, below). Since many psychotropics are metabolized by the cytochrome P450 system (Nemeroff et ah, 1996), which in turn can be inhibited by the SSRIs, caution should be exercised when combining agents, such as the TCAs, with SSRIs. 

A number of successful case reports, open trials and randomized controlled trials have been published with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, paroxetine, and fluvoxamine in the treatment of adult PTSD (see reviews by Connor and Davidson, 1998 Hidalgo and Davidson, 2000). Two SSRIs, fertraline and paroxtine, have recently received FDA approval for treatment of PTSD in adults (Brady et ah, 2000 Marshal et al., 2001). Surprisingly, there are no reports of the use of SSRIs in pediatric... 

In this chapter, we review the pharmacology of several selective serotonin reuptake inhibitors [SSRIs] and other drugs that act on the serotonergic system. That these developments have enhanced safety and tolerability is now beyond dispute, but it is also clear that these agents are no more effective than the old-style tricyclic antidepressants [TCAs]. [For a comprehensive discussion of serotonergic medication, see Montgomery, Chapter 12, in this volume.] Here, several compounds are discussed in detail. 

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