Orthostatic hypotension with antidepressants

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

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... 

A number of medications have been associated with an increased risk of falling, including drugs affecting mental status such as antipsychotics, benzodiazepines, tricyclic antidepressants, sedative-hypnotics, anticholinergics, and corticosteroids. Some cardiovascular and antihypertensive drugs also can contribute to falls, especially those causing orthostatic hypotension.9... 

Use caution in patients with a recent history of Ml or unstable heart disease. Bupropion was well tolerated in depressed patients who had previously developed orthostatic hypotension while receiving tricyclic antidepressants and was generally well tolerated in depressed patients with stable CHF. Bupropion was associated P.784... 

Altered homeostasis in older persons can lead to important and common adverse drug effects the less robust homeostatic milieu may be stressed by drugs, causing adverse effects. Examples include orthostatic hypotension due to antihypertensives and other agents that cause a-adrenergic blockade (e.g. terazosin, doxazosin, tricyclic antidepressants and phenothiazines) in those with barorecep-tor dysfunction. Diuretics can cause hyponatraemia or hypokalaemia in older patients, whereas ACE inhibitors and NSAIDs can cause hyperkalaemia. 

Trazodone is an older antidepressant that is associated with significant sedation. Currently, trazodone is not recommended as a first-line antidepressant because of an increased risk of orthostatic hypotension, arrhythmias, and priapism. Also, compared with other available antidepressants, trazodone does not offer an advantage in terms of therapeutic efficacy. However, trazodone may be useful in patients with insomnia. It is currently common practice to use low doses of trazodone (e.g., 50-100 mg) to assist with initial insomnia while starting treatment with one of the newer antidepressants to address the underlying depression. If this strategy is used, we recommend tapering the trazodone dose and discontinuing treatment with trazodone after 4—6 weeks. 

Bupropion, the only marketed aminoketone antidepressant, also has a side-effect profile different from the other classes of antidepressants. It is essentially devoid of anticholinergic, antihistaminic, and orthostatic hypotensive effects. Its principal adverse effects are consistent with its indirect agonism of dopamine and NE via uptake inhibition and include the following ... 

One old-fashioned augmentation strategy that has fallen out of favor in recent years is to combine with great caution a TCA and an MAO inhibitor (the cautious combo in Fig. 7—30). Given its potential dangers (e.g., sudden hypertensive episodes, orthostatic hypotension, drug and dietary interactions, obesity), as well as the wide variety of other antidepressant combinations available today, this combination is rarely necessary or justified. 

The adverse effects of moclobemide have been well reported in several studies, mainly comparisons of moclobemide with standard antidepressants. The consensus has been that moclobemide produces fewer anticholinergic effects and less orthostatic hypotension and dizziness than clomipramine or imipramine. The main problems... 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

Answer C. Orthostatic hypotension occurs with both tricyclic antidepressants and phe-nothiazines because both types of drug can block alpha adrenergic receptors in venous beds. Their ability to block M receptors leads to xerostomia (not salivation) and mydriasis (not miosis). THcyclics and phenothiazines also share a common tendency to decrease seizure threshold and cause weight gain (not loss). 

Phenethylhydrazine (Nardil) appears to act more specifically as an antidepressant (8) inasmuch as no antihypertensive or antianginal effects have been reported. Instances of orthostatic hypotension have been described, but these effects appear to be more variable and less intense than with a -methyl-phenethylhydrazine. 

Their exact mode of action in depressed states is unknown. It is doubtful if monoamine oxidase inhibition is the only basis of their antidepressant effect. Certainly, potent antidepressant agents are available which exhibit no effect on monoamine oxidase. It is, of course, possible and probable that there are several means of relieving depression, of which monoamine oxidase inhibition is one. Although the agents in use now are much less toxic than the older preparations, they must be given with caution, since hepatitis, severe orthostatic hypotension,... 

Insomnia caused by major psychiatric illnesses often responds to specific pharmacological treatment for that illness. In major depressive episodes with insomnia, for example, the selective serotonin reuptake inhibitors, which may cause insomnia as a side effect, usually will result in improved sleep because they treat the depressive syndrome. In patients whose depression is responding to the serotonin reuptake inhibitor but who have persistent insomnia as a side effect of the medication, judicious use of evening trazodone may improve sleep, as well as augment the antidepressant effect of the reuptake inhibitor. However, the patient should be monitored for priapism, orthostatic hypotension, and arrhythmias. 

ADVERSE EEEECTS Tricyclic antidepressants routinely produce adverse autonomic responses, in part related to their relatively potent antimuscarinic effects, including dry mouth and a sour or metallic taste, epigastric distress, constipation, dizziness, tachycardia, palpitations, blurred vision (poor accommodation and increased risk of glaucoma), and urinary retention. Cardiovascular effects include orthostatic hypotension, sinus tachycardia, and variable prolongation of cardiac conduction times with the potential for arrhythmias, particularly with overdoses. 

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