Comparative Side Effect Profiles of Trazodone and Imipramine: Special Reference to the Geriatric Population

Abstract

Side effects are a concomitant of almost all therapeutic agents and are also present as part of the pharmacological profile of psychotropic agents. However, the laboratory pharmacological characteristics of agents are a more reliable predictor of side effect profiles than they are of their therapeutic activities. Therefore, it would seem possible to be able to predict with much greater accuracy the clinically significant side effects that may be encountered from the preclinical data. This has been established in the case of trazodone and imipramine. The anticholinergic profile of imipramine was clearly determined in the laboratory and in man it produces a range of activity varying from mild peripheral anticholinergic activity to impairment of various functions involving vision, cardiovascular function and gastrointestinal activity. However, in the geriatric population, because of the vast amount of research implicating cholinergic mechanisms in memory functions and particularly in some aspects of cognitive deficit, it may be predicted that the anticholinergic activity of the tricyclics may present an especially troublesome pattern in a geriatric population that requires antidepressant therapy. These comparative effects between the two agents will be discussed and documented from control study data.

Trazodone in late life depressive states: a double-blind multicenter study versus amitriptyline and mianserin

“…TRZ is a relatively new antidepressant agent and some literature studies have shown its safety in treating elderly depressive situations (Gershon 1984;Burns et al 1986). Also for TRZ, pharmacokinetic studies showed a prolonged half-life with a larger area under the plasma concentrationtime curve and a reduced oral clearance in the elderly compared to younger subjects (Bayer et al 1983).…”

“…As previously stated, this is a factor that can indirectly influence clinical outcome, and the choice when treating the elderly should be mostly focused on the search for a compound which scarcely aggravates the pre-existing functional cerebral and extra-cerebral impairments. TRZ seems to produce fewer overall side effects than does imipramine and causes few or no anticholinergic or cardiovascular side effects (Gershon 1984). Moreover, some authors report that cognition and performance are less adversely affected in geriatric subjects by TRZ than by amitriptyline (Burns et al 1986).…”

United States Experience with Trazodone: A Literature Review

“…Clinicians are placed in a precarious posi tion when prescribing antidepressant medi cations that are potentially lethal in overdose -including TCA agents and the monoamine oxidase (MAO) inhibitors -to patients with depressive disorders who are at high risk for suicide attempts. It is important to note that trazodone was one of the first antidepressant drugs for which animal studies indicated rel ative safety in overdose conditions [28][29][30]. Indeed, despite over 2.5 million patients having received trazodone since 1982, there is not a single documented case of lethal overdose caused directly by trazodone alone.…”

“…First, the sedation ex perienced by about half of the patients tak ing trazodone can be helpful to anxious indi viduals or to those suffering from insomnia, but in some patients this sedation effect can cause discomfort [7,11,28,29]. Second, similar to most TCA-type agents, trazodone is reported to produce orthostatic hypoten sion; the problem can be minimized by hav ing patients take the drug on a full stomach to slow down absorption, or by having them consume the major portion of the drug be fore going to bed [11,38] In summary, trazodone has an intriguing side-effect profile.…”

Confirmation of the Neurophysiologically Predicted Therapeutic Effects of Trazodone on Its Target Symptoms Depression, Anxiety and Insomnia by Postmarketing Clinical Studies with a Controlled-Release Formulation in Depressed Outpatients

“…Clinical trials in the 1980s made trazodone the most widely prescribed antidepressant in the USA [16], which was mainly due to its good tolerability, especially in the elderly [17], its hypnotic properties in depression [9,18], dysthymia [10,19], SSRI-induced insomnia [20], sleep apnea [21] and benzodiazepine dependency [22,23] as well as its anxiolytic properties [24,25]. Trazodone was further found to be clinically useful after discontinuation of chronic benzodiazepine therapy [26], in agitation and hostility of patients with dementia and organic disorders [27], negative symptoms of chronic schizophrenia [28][29][30], bulimia nervosa [31], erectile dysfunction [32], tremor and iatrogenic dyskinesias [33,34], alcoholism [35] and chronic pain disorders [36].…”