Trazodone side effects

Two rather broad structural classes account for the large majority of drugs that have proven useful in the clinic for treating depression. Each of these has associated with it some clearly recognized side effects the monoamine oxidase inhibitors, most commonly derivatives of hydrazine, tend to have undesirable effects on blood pressure the tricyclic compounds on the other hand may cause undesirable changes in the heart. Considerable effort has thus been expended toward the development of antidepressants that fall outside those structural classes. An unstated assumption in this work is the belief that very different structures will be associated with a novel mechanism of action and a different set of ancillary activities. One such compound, trazodone... 

Trazodone and nefazodone cause minimal anticholinergic effects. Sedation, dizziness, and orthostatic hypotension are the most frequent dose-limiting side effects. 

Trazodone, 25 to 100 mg, is often used for insomnia induced by selective serotonin reuptake inhibitors or bupropion. Side effects include serotonin syndrome (when used with other serotonergic drugs), oversedation, a-adrenergic blockade, dizziness, and rarely priapism. 

In 2002, the Supreme Judicial Court of Massachusetts joined a growing number of state courts that have recognized a responsibility of pharmacists to warn patients of possible side effects from prescribed medications. In the case of Cottam v. CVS Pharmacy (764 N.E.2d 814), that court affirmed a jury verdict in favor of a patient who had not been warned of the risk of priapism by the pharmacist who dispensed trazodone to him. The facts of the case disclosed that the pharmacy provided a short list of warnings to the patient but priapism was not included on the list. The court ruled that when a patient can reasonably conclude that a list of side effects is a complete and comprehensive list, the pharmacy has undertaken a legal duty to provide complete warnings and information. 

Trazodone (Desyrel). Trazodone was the first of the atypical antidepressants and was actually introduced prior to the SSRIs. It does not have the serious cardiac toxicity or anticholinergic side effects of the TCAs and was the most popular antidepressant until the arrival of the SSRIs. It is approved for the treatment of depression and is also commonly used in low doses to treat agitation in demented patients and insomnia. 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

When we talk about serotonin-blocking medications, a point of clarification must be made. In most cases, medications do not block overall serotonin activity but instead block the activity at one of the many serotonin receptor types. For example, the antidepressants trazodone, nefazodone, and mirtazapine increase total serotonin activity yet they block certain of the serotonin receptors. Mirtazapine increases both serotonin and norepinephrine activity by interfering with the alpha-2 receptor. By also blocking the serotonin-2 and serotonin-3 receptors, mirtazapine avoids the sexual dysfunction and GI side effects commonly experienced with other serotoninboosting medications. We cannot truly call these serotonin-blocking medications, because they are serotonin-boosting medications that selectively block certain serotonin receptors. 

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

Histamine blockade is responsible for the sedation associated with trazodone. Furthermore, priapism and orthostatic hypotension are mediated by a-adrenergic antagonism. There have been over 200 case reports of priapism (Thompson et ah, 1990). Prevalence estimates of priapism suggest that 1/6000 men treated with trazodone will be affected. Other side effects include dry mouth, nausea, and vomiting. Because of trazodone s wide therapeutic window, it is relatively safe in overdosage. There are case reports of patients surviving intentional overdoses of up to 9 (Gamble and Peterson,... 

It is difficult to justify, therefore, any use of trazodone in boys, adolescent males, or young men, especially given its relatively limited usefulness as an antidepressant or even a sedative. Even in girls its use is questionable. Nefazodone would appear to be a far better alternative, especially in that it has no recognized sexual side effects, is well tolerated once the patient adapts to the sedative effect, and is not associated with priapism. That is, risks do not include a known increase in priapism above the background incidence (Thompson et ah, 1990 Feiger et ah, 1996 Pecknold and Langer, 1996). 

Excessive sedation is the most commonly encountered side effect of trazodone. Although trazodone has virtually no anticholinergic side effects, dry mouth and blurred vision occur more frequently with trazodone treatment than with placebo. 

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. 

Nefazodone has a chemical structure related to trazodone and incorporates both 5-HT uptake properties plus 5-HT 2a receptor blockade (150, 151, 152 and 153). There is evidence from controlled trials that this agent is an effective antidepressant with a favorable side-effect profile. 

Other antidepressant drugs that primarily affect serotonin reuptake include trazodone [TRAZ oh done], fluvoxamine [floo VOX a meen], nefazodone [ne FAZ oh don], paroxetine [pah ROX a teen], sertraline [SIR trah leen], and venlafaxine [vin lah FACKS in]. These SSRIs differ from fluoxetine in their relative effects on the reuptake of serotonin and norepinephrine. They do not seem to be more efficacious than fluoxetine, but their profiles of side effects are somewhat different. There is a high variability among patients in the rate of elimination of these drugs (including fluoxetine), and failure to tolerate one drug should not preclude a trial of another SSRI. 

The correct answer = B The tricyclic antidepressants and especially imipramine are effective in this condition because it contracts the internal sphincter of the bladder. Fluoxetine and trazodone act at serotonin receptors and have no effect on bladder function. Tranylcypromine is an MAO inhibitor with serious side effects. 

Fisher et al. (1993) conducted a phone survey of pharmacy patients taking various antidepressants and compared fluoxetine to trazodone. They concluded that fluoxetine caused a higher incidence of psychologic/ psychiatric adverse clinical events, including delusions and hallucinations, aggression, and suicidal ideation (p. 235, emphasis added). In a followup study, Fisher et al. (1995) found that many of the same side effects reported in regard to Prozac were also reported for Zoloft. Both drugs... 

Chan CH, Ruskiewicz RJ. Anticholinergic side effects of trazodone combined with another pharmacologic agent. Am J Psychiatry 1990 147(4) 533. 

Broom 2. Ginkgo biloba 3. Scopolia 4. Yohimbine 1. TCAs (e.g. amitriptyline, nortriptyline, clomipramine) 2. SSRIs (e.g. fluvoxamine fluoxetine, paroxetine) 3. Venlafaxine 4. Trazodone May develop cardiac arrhythmias and side-effects such as dryness of the mouth, retention of urine and tachycardia, t sedation Broom contains cardioactive alkalamines such as sparteine Inhibits metabolizing enzymes Anticholinergic properties (hyoscine present in scopolia may worsen side-effects of TCAs-additive antimuscarinic effects) Yohimbine alone can cause hypertension, but lower doses cause hypertension when combined with TCAs Unknown mechanism (ginkgo t sedative effects of trazodone) St John s wort inhibits the uptake of serotonin and thereby t serotonin levels Avoid concomitant use. An SSRI may be a better alternative to be used with broom... 

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