Amantadine

Adamantane (antiviral; glutamate NMDA antagonist, increases norephinephrine, higher doses increases dopamine)

  • Treatment Resistant Depression3
  • Bipolar Depression4
  • Antipsychotic side effects: Tardive dyskinesia2, extrapyramidal2, weight loss3
  • Autism3
  • OCD3
  • Irritability in TBI1
  • Child-DMDD3
  • Sexual dysfunction male4 and female4
  • Fatigue in medical illness or COVID3

Features

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Handout

Dosing

100-300 mg daily in divided doses, morning and noon, with greater dose given in morning. Raise by 100 mg per week.

Management

Ketamine-like effects and dopaminergic. Although not broadly effective for depression, some patients with high levels of treatment resistance have responded very well to it. Like ketamine, can cause intense spiritual feelings (advise patient with depression to engage more in something that inspires awe, beauty, spirituality).

TOLERABILITY: Warn patient that 1 in 10 people don’t tolerate it for various reasons, headache, dizziness.

RISKS: Edema, caution in heart disease (CHF). Delirium, hallucinations.

EMR Text

Major Depression

Amantadine use based on small randomized and open-label trials in depression (Vale S et al, Lancet 1971;2(7721):437).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Bipolar Depression

Amantadine use based on open-label trials in bipolar disorder (where it improved depression and may reduce mania) and small randomized trials in general depression (Krzystanek M et al, Pharmaceuticals (Basel). 2020;13(10):326; Ohlmeier MD et al, Pharmacopsychiatry 2008;41(5):202-203; Vale S et al, Lancet 1971;2(7721):437).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

OCD

Amantadine use based on a randomized trial in OCD (Naderi S et al, Psychiatry Clin Neurosci. 2019; 73(4):169-174).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Disruptive mood (DMDD)

Amantadine use based on a open label evidence in disruptive mood dysregulation disorder (as well as controlled trials in child and adult populations where it improved similar symptoms like irritability) (Rice T et al, J Child Adolesc Psychopharmacol 2019;29(8):642-646).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Traumatic brain injury (TBI)

Amantadine use based on large randomized trials in TBI where it improved irritability and functioning (Hammond FM et al, PM R. 2024;16(7):661-668).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Autism

Amantadine use based on randomized trials where it improved hyperactivity, irritability, and inappropriate speech in autism (in other studies it improved cognition, OCD, mood, and energy) (Mohammadi MR et al, Clin Neuropharmacol. 2013;36(6):179-184).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Extrapyramidal side effects (EPS, parkinsonism)

Amantadine use based on trials where it improved extrapyramidal side effects on antipsychotic (Wisidagama S et al, Medicines (Basel). 2021;8(6):24).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Tardive Dyskinesia

Amantadine use based on trials where it improved extrapyramidal side effects on antipsychotic (Wisidagama S et al, Medicines (Basel). 2021;8(6):24).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

Fatigue from medical illness or COVID

Amantadine use based on trials where it improved fatigue related to medical illnesses and long-COVID (Harandi AA et al, Sci Rep. 2024;14(1):1343).

Amantadine side effects, including delirium/hallucinations, reviewed with patient.

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