Efficacy of Antidepressants for Depression in Alzheimer’s Disease (AD)

AD is a neurodegenerative disease comprised of chronic, debilitating progressive symptoms & functional decline. With AD advancement, neuropsychiatric symptoms like depressive symptoms, psychotic symptoms, sleep impairment & behavioral disturbances develop. At an early stage of AD, common non-cognitive depressive symptoms precipitate, & behavioral disturbances are noticed at a later stage. The prevalence of depressive symptoms of AD ranges from 30% to 50% causing severe neuropsychiatric symptoms, and loss of serotonin receptors & transporters. Consistent depressive symptoms induce behavioral disturbance risk & lower quality of life. Administration of effective appropriate treatment may partially reverse complications. Pharmacological therapy, psychosocial interventions & electroconvulsive therapy are considered the prominent treatment for depression-associated AD.

Risk factors for AD-associated depression

1. Vascular complications

2. Neuroimaging changes in white matter hyperintensities or leukoencephalopathy, affecting the frontal striatal & frontal-limbic brain pathways

3. Family history & incidence of prior depression episodes

4. ApoE4 positivity

5. Usage of certain medications like beta-blockers, corticosteroids, & benzodiazepines

6. Prolonged exposure to dopamine agonists, stimulants, anticonvulsants, hormone-altering drugs, proton pump inhibitors & H2 blockers, statins or lipid-lowering drugs, & anticholinergic

Efficacy and safety of antidepressants in AD

Antidepressants are the backbone of treatment for AD patients with depression. This is due to the scarcity of alternative treatment options & the positive perception of antidepressants.

For the past 30 years, small randomized, double-blind, placebo-controlled clinical trials with disputable & conflicting results are being used to evaluate the efficacy & safety of antidepressants in AD-associated depression.

Tricyclic and tetracyclic antidepressants

Imipramine, clomipramine, maprotiline, amitriptyline, desipramine & mianserine

• No positive influence on cognitive status over the course of treatment

• Low tolerability than selective serotonin reuptake inhibitors (SSRIs) & serotonin - norepinephrine reuptake inhibitors (SNRIs).

Selective serotonin reuptake inhibitors (SSRIs) Sertraline

• Improve depression symptoms

• No negative effects on the cognitive status

• Sustainable tolerability

Citalopram and Escitalopram

• Good tolerability

Fluoxetine

• Significant improvement in depressive symptoms

• Proven efficacy • No cognitive alternation

• Good tolerability

Paroxetine

• No promising effectiveness • Good tolerability

Serotonin-norepinephrine reuptake inhibitors (SNRIs) Venlafaxine

• Efficacy not confirmed • Absence of favourable tolerability

Noradrenergic and specific serotonergic antidepressants (NaSSAs)

• Effectively reduce depression symptoms

• Moderate tolerability

Reversible inhibitors of monoamine oxidase A (RIMAs)

Moclobemide

• Effective in AD-associated depression

• Well tolerated & with favourable outcomes on cognitive status

Serotonin modulators and stimulators (SMS)

Vortioxetine

• Established good tolerability

• Proven effect on cognitive performances

Side effects of antidepressants

1. Hyponatremia

2. Cardiotoxicity

3. Increased bleeding tendency

Conclusion

The correct benefit of antidepressants in the treatment of AD-associated depression demands authentic supportive controlled clinical trials with rigorous & similar methodology, increased sample size and homogeneity between patients. Advice should be to opt for, SSRIs, specifically sertraline, which can be used as the primary therapeutic agent indicated for depression in AD because it has an acceptable tolerability profile despite its unclear efficacy. Tri and tetra-cyclic antidepressants should be avoided as they have a controversial efficacy & reduced tolerability.

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