Antidepressants adverse effects

Oral contraceptives reduce the clearance of imipramine, probably by reducing hepatic oxidation, and thus increase its half-life. Hydroxylation of amitriptyline is inhibited by contraceptive steroids. The clinical significance is uncertain, but there is at least anecdotal evidence of an increase in antidepressant adverse effects (360). Caution should be exercised when tricyclic antidepressants are used long term in women taking oral contraceptives. 

The FDA provided a summary of 52 adverse psychiatric reactions reported over the prior year for Concerta and Ritalin, including cases of overstimulation (agitation and mania), depression, psychosis, aggression and violence, and suicidal behavior (FDA, 2006b). Notice the similarity to the dangerous effects that the FDA previously recognized as associated with the newer antidepressants. The similarity between stimulant and antidepressant adverse effects is probably due to the stimulating effects of the newer antidepressants. 

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. 

Second-Generation Antidepressants. The frequency of adverse effects associated with first-generation antidepressants and the lack of patient compliance arising from such adverse effects led to the development of a number of second-generation antidepressants. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Side Effects and Toxicity. Adverse effects to the tricycHc antidepressants, primarily the result of the actions of these compounds on either the autonomic, cardiovascular, or central nervous systems, are summarized in Table 3. The most serious side effects of the tricycHcs concern the cardiovascular system. Arrhythmias, which are dose-dependent and rarely occur at therapeutic plasma levels, can be life-threatening. In order to prevent adverse effects, as weU as to be certain that the patient has taken enough dmg to be effective, the steady-state semm levels of tricycHc antidepressant dmgs are monitored as a matter of good practice. A comprehensive review of stmcture—activity relationships among the tricycHc antidepressants is available (42). 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Mannion V Case report adverse effects of taking tricyclic antidepressants and smoking marijuana. Can Earn Physician 45 2683—2684, 1999... 

Wilens TE, Biederman J, Spencer TJ Case study adverse effects of smoking marijuana while receiving tricyclic antidepressants. J Am Acad Child Adolesc Psychiatry 36 481 85, 1997... 

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Psychiatric adverse effects occur frequently and may include irritability, depression, and rarely, suicidal ideation. Individuals with a history of uncontrolled psychiatric disorders must weigh the risk versus benefit of treatment, as interferon may exacerbate or worsen the psychiatric condition. Patients who develop mild to moderate symptoms may require antidepressants or anxiolytics. Those with severe symptoms including suicidal ideation should have the treatment discontinued immediately.43... 

Differentiate antidepressants according to pharmacologic properties, adverse-effect profiles, pharmacokinetic profiles, drug interaction profiles, and dosing features. 

Predict adverse-effect profiles of antidepressants based on pharmacology. 

The important adverse effects of the various antidepressants are often a function of their underlying pharmacologic profiles7,8 (Table 35-3). TCAs cause problematic sedative, anticholinergic, and cardiovascular adverse effects owing to their interaction with dirty receptors. While these adverse effects generally are considered to be common and bothersome, they can be quite serious in certain cases. For example, constipation in its... 

Trazodone routinely causes sedation, which is why it is used far more often as an adjunct with other antidepressants for sleep than as a primary agent for the treatment of depression. Priapism is a rare but serious adverse effect in males who take trazodone. In addition, orthostatic hypotension and dizziness are more common with trazodone than with nefazodone because the latter agent has a weaker effect at a-adrenergic receptors and also has a balancing of adrenergic effects owing... 

The relative incidence of adverse effects among some of the newer antidepressant agents are shown in Table 35-4.9,13,28... 

Several antidepressants, including most of the SSRIs, nefa-zodone, and duloxetine, are known to inhibit various cytochrome P-450 isoenzymes, thereby elevating plasma levels of substrates for those isoenzymes and thus potentially leading to increased adverse effects or toxicity of those drugs. The propensity to cause these drug interactions will vary with the particular antidepressant and the precise isoenzyme9,19,30 (Table 35-6). 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

Imipramine treatment resulted in a higher rate of remission of anxiety symptoms than trazodone, diazepam, or placebo (e.g., 73% versus 69% versus 66% versus 47%) in an 8-week controlled trial of DSM-III-diagnosed GAD patients. Antidepressants were more effective than diazepam or placebo in reducing psychic symptoms of anxiety. The use of TCAs generally is limited by bothersome adverse effects (e.g., sedation, orthostatic hypotension, anticholinergic effects, and weight gain). 

Evaluate patients for symptom improvement frequently (e.g., weekly) during the first 4 weeks of therapy. The goal is to alleviate panic attacks and reduce anticipatory anxiety and phobic avoidance with resumption of normal activities. Alter the therapy of patients who do not achieve a significant reduction in panic symptoms after 6 to 8 weeks of an adequate dose of antidepressant or 3 weeks of a benzodiazepine. Regularly evaluate patients for adverse effects, and educate them about appropriate expectations of drug therapy. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

Ferguson, James M., SSRI Antidepressant Medications Adverse Effects and Tolerability , The Primary Care Companion to The Journal of Clinical Psychiatry 3, no. 1 (2001) 22-27... 

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