Side effects newer antidepressants

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

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. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Mirtazapine (Remeron) is a newer antidepressant that also blocks 5-HT reuptake, but additionally has antagonistic effects at adrenergic o2, 5-HT2, and 5-HT3 receptors (Stahl 1998). Mirtazapine appears to have indirect agonistic effects on 5-HTlA receptors, which may contribute to its antidepressant effect (Berendsen and Broekkamp 1997). Nefazodone, as well, has SSRI and 5-HT2 antagonist effects. The 5-HT2 antagonist effects of these antidepressants is believed to be responsible for their lower incidence of sexual side effects (Nutt 1997). 

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

The fifth factor is the potential for side effects. In general, the newer antidepressants have less cumbersome side effects than the older agents. Your patients should be informed of potential side effects when selecting an antidepressant. By discussing side effects in advance, your patient may help you to decide which side effects would be most distressful to him/her. For example, dizziness may be a problem for an elderly patient at risk for falls, and sexual side effects may be more concerning to others. 

For whatever reason, few controlled trials of antidepressants have been performed in the treatment of dysthymic disorder. The limited evidence available, however, suggests that the same classes of antidepressants that effectively treat major depression also treat dysthymia. Reported side effects are similar with the newer agents tolerated better than TCAs. 

Atypicai Antipsychotics. In the 1980s and early 1990s, the SSRIs began a revolution in the treatment of depression. Tried-and-true but side effect laden tricyclic antidepressants fell into disfavor as newer and safer medications became available. A similar revolution is taking place in the treatment of psychosis. A new generation of antipsychotics that have fewer of the more disturbing side effects and may well be more effective are now available. 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Although studies suggest that antidepressants of any class are efficacious for the treatment of BN, the favorable side effect profile and lower toxicity of the newer generation antidepressants make their use preferable. Of these, fluoxetine is the best studied and is the only antidepressant at this time with FDA approval for the treatment of BN. 

When treating insomnia without depression, doxepin and amitriptyline (both tricyclic antidepressants) can be administered in low doses (25-100 mg) at bedtime. These antidepressants, however, do have troublesome anticholinergic side effects (dry mouth, constipation, blurred vision, dizziness) and adverse effects on the heart, and they can be lethal if taken in overdose. Because of their effect on heart function, these antidepressants should be avoided in patients with heart problems and administered cautiously, if at all, to those who are already receiving one of any number of newer antidepressants that inhibit the metabolism of the TCAs. 

Tricyclic antidepressant medications were developed in the 1950s and 1960s. Because they affect multiple neurotransmitters in the brain, they are thought to have more side effects than the newer class of SSRIs, which target the specific neurotransmitter serotonin. 

Newer antidepressants (such as the SSRIs, bupropion, and venlafaxine] probably achieved their impressive popularity primarily because their side-effect profiles were more favorable. Because dry mouth, blurry vision, tachycardia, lethargy, constipation, urinary hesitancy, and arrhythmias are deeply distressing to many, paucity of anticholinergic side effects from SSRIs was especially noteworthy. Convenience and simplicity of use are also favorable qualities for some newer agents. However, the decreased libido, anorgasmia, and erectile problems caused by SSRIs are of note and should be taken into consideration for long-term therapy. 

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. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Table 1.7 The most common side effects of SSRIs, SNRIs and other newer antidepressants (Sadock and Sadock, 2001)...

As mentioned in Chapter 2, another side effect of these newer types of antidepressants is that they can cause people to show signs of REM behavior disorder, which is characterized by periodic moments of acting out dreams. Rather than having the person stop taking the antidepressant altogether to avoid this, many times a doctor will prescribe a benzodiazepine such as clonazepam (Klonopin) that helps to suppress the REM behavior disorder symptoms. 

Problems and side effects associated with buspirone include dizziness, headache, nausea, and restlessness. Antidepressants such as paroxetine and venlafaxine also produce a number of side effects (described in Chapter 7) depending on the specific agent. Nonetheless, these newer, nonbenzodiazepine... 

In the past, tricyclic drugs such as amitriptyline and nortriptyline were the most commonly used antidepressants and were the standard against which other antidepressants were measured.30 The use of tricyclic drugs as the initial treatment of depression has diminished somewhat in favor of some of the newer second-generation drugs, which may have more favorable side-effect profiles. Tricyclic agents, nonetheless, remain an important component in the management of depressive disorders, especially in more severe forms of depression that fail to respond to other antidepressants.6,53... 

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