From the Guidelines
Tricyclic antidepressants (TCAs) can have a significant negative impact on cognition, particularly in older adults, due to their anticholinergic properties, and should be used with caution or avoided when possible, especially in favor of alternatives like SSRIs or SNRIs. The cognitive effects of TCAs, such as confusion, memory impairment, difficulty concentrating, and mental fogginess, are thought to be dose-dependent, with higher doses causing more pronounced cognitive impairment 1. Some key points to consider when evaluating the cognitive effects of TCAs include:
- The anticholinergic properties of TCAs, which can disrupt memory formation and cognitive processing
- The increased vulnerability of older adults to these effects due to age-related changes in brain chemistry and metabolism
- The variability in anticholinergic effects among different TCAs, with nortriptyline and desipramine generally causing fewer cognitive problems than amitriptyline or imipramine 1
- The potential for cognitive side effects to be reversible when the medication is discontinued or the dose is reduced
- The availability of alternative antidepressant medications with fewer anticholinergic properties, such as SSRIs (e.g., fluoxetine, sertraline) or SNRIs (e.g., venlafaxine, duloxetine), which may help preserve cognitive function while still treating depression. In clinical practice, it is essential to weigh the potential benefits of TCAs against their potential cognitive risks, particularly in older adults, and to consider alternative treatment options when possible.
From the FDA Drug Label
Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia
The cognitive effects of TCA (tricyclic antidepressant) overdose include:
- Confusion
- Disturbed concentration
- Agitation
- Drowsiness
- Stupor These effects are a result of the CNS depression caused by TCA overdose, as reported in the drug labels of nortriptyline 2 and imipramine 3.
From the Research
TCA and Cognition Effects
- Tricyclic antidepressants (TCAs) have been found to have a negative impact on cognitive function compared to selective serotonin reuptake inhibitors (SSRIs) 4.
- TCAs can cause anticholinergic, hypotensive, or sedating reactions, which may impair cognitive function 4.
- A systematic review found that TCAs do not have procognitive effects, whereas vortioxetine and bupropion have demonstrated procognitive effects in major depressive disorder (MDD) populations 5.
- Non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also shown significant positive effects on cognition in depression 5.
Comparison with Other Antidepressants
- A study comparing amitriptyline with other tricyclic/heterocyclic antidepressants and SSRIs found that amitriptyline was at least as efficacious as other tricyclics or newer compounds, but had a greater burden of side-effects 6.
- Another study found that SSRIs had a more favorable safety profile than TCAs in both acute and long-term treatment of major depression 4.
- A systematic review and meta-analysis found that both SSRIs and TCAs were efficacious in the treatment of chronic depression, but SSRIs showed better acceptability in terms of dropout rates 7.
Cognitive Impairment in MDD
- A systematic review found that present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed 5.
- Further research is needed to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD 5.