Depression and the Pharmacology of Antidepressant Drugs Flashcards: Set 7

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Most common reason for treatment failure for TCA-type antidepressants:Inadequate trial. A full trial is described as giving the maximum daily dosage (tolerable) for at least six weeks.
Dosing approach for use of TCA-type drugs and treatment of panic disorder:Treatment should be initiated with very low doses, then increased slowly.
Cautions involving TCAs with respect to their anticholinergic (antimuscarinic) properties:Using atropine as a reference point for antimuscarinic activity, amitriptyline at 100 mg is thought to be the equivalent to atropine at 5 mg. The anticholinergic (antimuscarinic) property of TCAs requires that they be used with caution in men with prostatic hyperplasia (BPH). Anticholinergic effects may contribute other medical issues including heatstroke, constipation or dental difficulty secondary to dry-mouth (xerostomia).
Cardiac actions of TCAs-mechanisms:Some cardiac problems are due directly to drug anticholinergic action. Other effects are related to TCA-mediated "quinidine--like effects" which lead to myocardial depression. Other cardiac effects may be due to interference with adrenergic neurons. These various mechanisms of action result in altered rate (chronotropism), altered rhythm, and altered contractility (inotropism). Some of these changes are particularly important in those patients with pre-existing cardiac disease manifesting, for example, as bundle-branch or bifascicular conduction blockade. A range of ECG (electrocardiographic) changes have be described, including benign ST segment and T wave changes, sinus tachycardia, and complex, serious arrhythmias.
"Quinidine-like" effects of TCAs and patient management:TCAs have class I antiarrhythmic effects, often described as "quinidine-like". Accordingly, these agents should be used cautiously in individuals with known arrhythmias, cardiac conduction pathologies, or ischemic myocardial disease. Possibly for these individuals, SSRIs or atypical antidepressant drugs would be more appropriate initial treatment choices.
Tricyclic antidepressant medications (TCAs) and seizures:TCAs tend to decrease seizure threshold which may be a concern for those patients at risk for seizures including patients with prior head injury or who are in alcohol withdrawal..
TCAs and sexual dysfunction:TCA administration may result in a variety of sexual dysfunctions including erectile, orgasmic, and ejaculatory dysfunction. Along with these effects a reduction in libido is common as well. These side effects may well reduce patient compliance.
Abrupt discontinuation of tricyclic antidepressant medications (TCAs):Occasionally abrupt discontinuation may induce "cholinergic rebound" which presents as headaches and nausea with abdominal cramping.
TCAs and overdose:Overdoses of TCAs tend to be serious, given its narrow therapeutic index (TD50/ED50). The therapeutic index is thus the ratio of the toxic dose for 50% of the population divided by the effective dose for 50% of the population. "Quinidine-like" effects on the heart are especially important in the overdose setting.
MAOI (monoamine oxidase inhibitor)-type antidepressants: first-line, second-line or third-line drugs?For management of depression, MAOI-type drugs are typically third-line medications. These agents might be used following treatment failures of SSRIs, TCAs, or atypical-type antidepressants. MAOI-agents have a number of adverse side effects and also dietary restrictions based on their ability to inhibit tyramine inactivating enzymes in the G.I. tract. Such inhibition can result in systemic absorption of excessive tyramine present in some foods.
Examples of side effects associated with MAOI drug administration:Orthostatic hypotension which may be persistent, tachycardia (sympathomimetic activity), tremor, and sweating. Nausea, sexual dysfunction, and insomnia are common. MAO-caused insomnia may benefit from oral trazodone given at bedtime. CNS side effects include toxic psychosis and agitation. Dietary restrictions have been described in earlier Flashcard sets.
Examples of exogenous amines which should not be ingested by patients on MAOI inhibitors (especially MAO-A type inhibitors):Phenylephrine, meperdine, phenylpropanolamine, dextromethorphan, as well as pseudoephedrine. Some of these agents may be found in cold medications.
Issues in switching antidepressant drugs treatment:If treatment failure occurs following an appropriate trial with the first chosen drug, a trial with a second drug would be appropriate. The correctness of the original diagnosis should be verified. Switching from one group of antidepressant drugs to one from another requires time for the concentration of the first drug to decline substantially. This period may be described as "washout time."
Examples of washout time when switching between antidepressant drug groups:A washout time of 2-3 weeks is required for transition from an MAO inhibitor to a TCA. In switching from an SSRI to an MAOI, about 4-5 week should be allowed. By contrast, switching within a group, such as from one TCA to another-e.g., imipramine to amitriptyline, washout time is not required.
Combination drug therapy in depression management:Sometimes lithium, buspirone, or thyroid hormone added to a regimen which includes an antidepressant drug may be useful. Possibly, low-dose atypical antipsychotics, as an adjunct drug, may help treat patients with refractory depression. Examples of such atypical agents include aripiprazole (FDA approved for this purpose), olanzapine, and risperidone. Adding an atypical agent likely requires additional monitoring, including body mass index, glucose, lipid levels.