Therapeutically used drugs antidepressants

Description of Method. Fluoxetine, whose structure is shown in Figure 12.31a, is another name for the antidepressant drug Prozac. The determination of fluoxetine and its metabolite norfluoxetine. Figure 12.31 b, in serum is an important part of monitoring its therapeutic use. The analysis is complicated by the complex matrix of serum samples. A solid-phase extraction followed by an HPLC analysis using a fluorescence detector provides the necessary selectivity and detection limits. 

I suppose that some ingenious minds will be able to find a way of accommodating the chemical-balance hypothesis to these data, but I suspect that the accommodation will require convoluted circumventions, like those used by the Flat Earth Society in their efforts to maintain their defunct theory in the face of photographic evidence from space. If depression can be equally affected by drugs that increase serotonin, drugs that decrease it and drugs that do not affect it at all, then the benefits of these drugs cannot be due to their specific chemical activity. And if the therapeutic benefits of antidepressants are not due to their chemical composition, then the widely proffered chemical-imbalance theory of depression is without foundation. It is an accident of history produced serendipitously by the placebo effect. 

Until the introduction of selective serotonin reuptake inhibitors (SSRIs) in the 1980s, tricyclic antidepressants were the most widely used drugs. The therapeutic effect of amitriptyline and imipramine are related to their ability to inhibit the presynaptic reuptake of both NA and 5-HT. They are referred to as non-selective reuptake inhibitors, whereas many of the other tricyclics are more selective thus, clomipramine is a selective reuptake inhibitor for 5-HT and desipramine and nortriptyline are selective... 

In contrast to the limited value of pharmacokinetics to the use of antidepressants, knowledge of the kinetics of lithium has been important in defining the therapeutic and toxic range in unipolar or bipolar manic patients. Prediction of the dose required by the individual patient by giving a single dose of the drug and measuring the erythrocyte/plasma lithium... 

DNLM 1. Mood Disorders—drug therapy. 2. Cognition Disorders—drug therapy. 3. Antidepressive Agents— therapeutic use. 4. Anti-Anxiety Agents— therapeutic use. WM 171 P5355 1999]... 

The commonly used classes of antidepressants are discussed in the following sections, and information about doses and half-lives is summarized in Table 2-1. The antidepressant classes are based on similarity of receptor effects and side effects. All are effective against depression when administered in therapeutic doses. The choice of antidepressant medication is based on the patient s psychiatric symptoms, his or her history of treatment response, family members history of response, medication side-effect profiles, and comorbid disorders (Tables 2-2 and 2-3). In general, SSRIs and the other newer antidepressants are better tolerated and safer than TCAs and MAOIs, although many patients benefit from treatment with these older drugs. In the following sections, clinically relevant information is presented for the antidepressant medication classes individually, and the pharmacological treatment of depression is also discussed. The use of antidepressants to treat anxiety disorders is addressed in Chapter 3. 

Rudorfer, M.V., Potter, W.Z. Antidepressants a comparative review of the clinical pharmacology and therapeutic use of the newer versus the older drugs. Drugs 37, 713-738, 1989. 

Experience with the SSRls predicts that as therapeutic actions of selective NRIs expand beyond antidepressant actions, the doses of drug, onsets of action, degrees of efficacy, and tolerability profiles may differ from one therapeutic use to another (Table 6-7 and 6—8). 

Although the specific pragmatic guidelines for use of these various therapeutic modalities for depression have not been emphasized, the reader should now have a basis for the rational use of antidepressant and mood-stabilizing drugs founded on application of principles of drug action on neurotransmission via actions at key receptors and enzymes. 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

Serotonin plays an active role in temperature regulation and in particular in the maintenance of the body s set point [543-545]. More recently, numerous pharmacological studies have suggested the involvement of homeostatic control mechanisms [544, 546] that are achieved through interplay between the 5-hydroxytryptamine (HT)1A and 5-HT2A/C receptor systems [545,547,548]. Administration of a 5-HTlA-receptor agonist that is used therapeutically as an antidepressant and antianxiety drug causes hypothermia [549,550]. 

Therapeutic uses The primary indication for fluoxetine is depression, where it is as effective as the tricyclic antidepressants. Fluoxetine is effective in treating bulimia nervosa and obsessive-compulsive disorder. The drug has been used for a variety of other indications, including anorexia nervosa, panic disorder, pain associated with diabetic neuropathy, and for premenstrual syndrome. 

The brain is the focus of this book but it is not the only organ injured by SSRI antidepressants. A recent study of 2,722 older women (mean age 78.5) found that the SSRIs drastically reduced their bone densities (Diem et al., 2007). The bone mineral density (BMD) decreased by 0.82% per year in SSRI users, compared to 0.47% in nonusers (p <. 001). On the other hand, women using tricyclic antidepressants had the same BMD as nonusers. One wonders how this form of SSRI toxicity might be rationalized as therapeutic. Meanwhile, it is yet one more reason not to prescribe the drugs, especially to older people. 

Like other drugs, psychotherapeutic drugs can be classified in different ways. The most common way is by therapeutic use, and the four major categories are antipsychotics, antidepressants, antianxiety agents, and mood-stabilizing drugs. 

Americans (26). It is involved in the metabolism of approximately 30-40 commonly used drugs. Millions of patients with compromised metabolism are thus at risk of adverse drug reactions when prescribed drugs that are CYP2D6 substrates. Many such drugs are used for treating psychiatric (such as antidepressants and antipsychotics) and cardiovascular diseases (such as j8-blockers and antiar-rhythmics), where the therapeutic window can be narrow and side effects common. 

If Wellbutrin is taken at a correct dose, it can be an effective antidepressant. It is an especially useful drug for those who have not responded to SSRI treatment. In one survey, it was the first choice of psychiatrists when patients did not improve while taking an SSRI. Furthermore, it is a safe and effective drug that can augment the therapeutic effects of other antidepressants (except MAOIs). For example, in one study, researchers looked at the addition of Wellbutrin in patients who took antidepressants with little success. Of patients who completed at least six weeks of Wellbutrin, 58 percent experienced remission of depression. 

While amphetamine had important antifatigue and moderate antidepressant properties, its therapeutic usefulness was severely limited because its stimulant action was followed by a depressive phase, tolerance to the drug developed, it depressed appetite, it tended to cause anxiety and jitteriness, and it had fairly potent effects on the cardiovascular system. 

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

While the SSRIs are the most frequently used drugs for treatment of major depressions, the tricyclics remain valuable alternatives. In some patients a tricyclic may be the first choice, especially if the past history indicates a positive therapeutic response to such drugs. The sedative actions of tricyclics may be of value in depressed patients with insomnia or weight loss, since SSRIs tend to exacerbate such symptoms. Generic formulations of the tricyclics are much less costly than any of the other antidepressant drugs. 

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