Is it okay to prescribe memantine (N-methyl-D-aspartate receptor antagonist) in addition to Selective Serotonin Reuptake Inhibitor (SSRI) as an augment for depression and dementia?

Memantine as an Augmentation to SSRIs for Depression and Dementia

Memantine should not be prescribed as an augmentation to SSRIs for depression in patients with dementia, as there is insufficient evidence supporting this combination for depression, and memantine should be reserved for moderate-to-severe Alzheimer's disease, Parkinson's disease dementia, Lewy body dementia, or vascular dementia. 1

Evidence for Memantine in Dementia

Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has established efficacy in specific dementia types:

• Approved for moderate-to-severe Alzheimer's disease
• Shows small but statistically significant benefits in:
  • Clinical global rating
  • Cognitive function
  • Activities of daily living
  • Behavior and mood 1, 2

The 5th Canadian Consensus Conference on Diagnosis and Treatment of Dementia (2020) recommends memantine specifically for:

• Alzheimer's disease (AD)
• Parkinson's disease dementia (PDD)
• Dementia with Lewy bodies (DLB)
• Vascular dementia (VD) 1

Memantine for Depression in Dementia

Current guidelines and evidence do not support using memantine as an augmentation strategy for depression in dementia:

• The 2017 consensus recommendations for management of rapid cognitive decline in Alzheimer's disease states that while combination therapy of cholinesterase inhibitors and memantine is rational and safe, evidence for recommending this combination is equivocal 1
• There is no strong evidence supporting memantine for treating depressive symptoms in dementia 3
• A 2021 study notes that while there is a belief that memantine may benefit depression, conclusive evidence is lacking 4

Potential Risks and Considerations

Adding memantine to an SSRI regimen presents several concerns:

1. Lack of evidence: No high-quality clinical trials support this specific combination for depression in dementia 3

2. Adverse effects: Memantine can cause:

   • Confusion
   • Dizziness
   • Falls
   • Headache 1, 2

3. Deprescribing considerations: Guidelines recommend discontinuing memantine if:

   • No clinically meaningful benefit is observed
   • The patient develops intolerable side effects
   • The patient has severe or end-stage dementia
   • Medication adherence is poor 1

Alternative Approaches

For patients with dementia and depression:

1. Optimize current dementia treatment:

   • Ensure optimal dosing of cholinesterase inhibitors if appropriate for the dementia type 1
   • Consider non-pharmacological interventions for both dementia and depression 5

2. Depression management:

   • Antidepressants should generally be reserved for individuals with depression where symptoms are distressing and meet the threshold for major depression 3
   • Pain management should be optimized as preliminary evidence supports adequate analgesia in improving mood in people with dementia 3

3. Non-pharmacological interventions:

   • Cognitive stimulation activities
   • Physical activity
   • Music therapy
   • Reminiscence therapy 5

Conclusion

While there is theoretical potential for glutamatergic modulation in depression 6, 4, the current evidence does not support prescribing memantine as an augmentation to SSRIs for depression in dementia patients. Memantine should be reserved for its approved indications in moderate-to-severe dementia of specific types (AD, PDD, DLB, VD), where it has demonstrated modest but significant benefits.