Possible Use of Amantadine in Depression

Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.

[1]  C. Parsons,et al.  Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents — preclinical studies , 1997, Neuroscience & Biobehavioral Reviews.

[2]  J. Kornhuber,et al.  Depression, Borna disease, and amantadine , 1997, The Lancet.

[3]  D. Dietrich,et al.  Amantadine and human Borna disease virus in vitro and in vivo in an infected patient with bipolar depression , 1997, The Lancet.

[4]  R. Dürrwald,et al.  First isolates of infectious human Borna disease virus from patients with mood disorders. , 1996, Molecular psychiatry.

[5]  W. Zimmermann,et al.  Borna disease virus genome transcribed and expressed in psychiatric patients , 1995, Nature Medicine.

[6]  W. Danysz,et al.  Potential antidepressive properties of amantadine, memantine and bifemelane. , 1993, Pharmacology & toxicology.

[7]  D. F. Thompson.  Amantadine in the treatment of cocaine withdrawal. , 1992, The Annals of pharmacotherapy.

[8]  S. Hendricks,et al.  Treatment of fluoxetine-induced anorgasmia with amantadine. , 1992, The Journal of clinical psychiatry.

[9]  P. Skolnick,et al.  1-aminocyclopropanecarboxylates exhibit antidepressant and anxiolytic actions in animal models. , 1991, European journal of pharmacology.

[10]  D. Ziedonis,et al.  Pharmacotherapy improves treatment outcome in depressed cocaine addicts. , 1991, Journal of psychoactive drugs.

[11]  C. Haertzen,et al.  Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. , 1991, NIDA research monograph.

[12]  J. Bormann,et al.  Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. , 1991, European journal of pharmacology.

[13]  P. Skolnick,et al.  Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. , 1990, European journal of pharmacology.

[14]  J. Bormann.  Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. , 1989, European journal of pharmacology.

[15]  J. Bormann,et al.  Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. , 1989, European journal of pharmacology.

[16]  J. Feather,et al.  Bromocriptine and amantadine in cocaine detoxification , 1989, Psychiatry Research.

[17]  R. Cohen,et al.  Amantadine treatment of fatigue associated with multiple sclerosis. , 1989, Archives of neurology.

[18]  R. Pillai,et al.  Amantadine and the end-stage dementia of Alzheimer's type. , 1989, Southern medical journal.

[19]  P. Jatlow,et al.  Desipramine facilitation of initial cocaine abstinence. , 1989, Archives of general psychiatry.

[20]  O. Appenzeller,et al.  Amantadine, fatigue, and multiple sclerosis. , 1988, Archives of neurology.

[21]  T. Maéno,et al.  Effects of memantine on the frog neuromuscular junction. , 1986, European journal of pharmacology.

[22]  J. Amsterdam,et al.  Borna Disease Virus: A Possible Etiologic Factor in Human Affective Disorders? , 1985 .

[23]  T. J. Murray,et al.  Amantadine Therapy for Fatigue in Multiple Sclerosis , 1985, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[24]  J. Amsterdam,et al.  Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. , 1985, Science.

[25]  J. Dunn,et al.  Pharmacological changes in dopaminergic systems induced by long-term administration of amantadine. , 1985, European journal of pharmacology.

[26]  R. Greenberg,et al.  Treatment of major depression and Parkinson's disease with combined phenelzine and amantadine. , 1985, The American journal of psychiatry.

[27]  Galbraith Aw.  Prevention of post-herpetic neuralgia by amantadine hydrochloride (Symmetrel). , 1983 .

[28]  J. Flaherty,et al.  Mental side effects of amantadine therapy: its spectrum and characteristics in a normal population. , 1981, The Journal of clinical psychiatry.

[29]  W. Shields,et al.  A prospective double-blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis. , 1980, The Journal of infectious diseases.

[30]  A. Monto,et al.  Prevention of Russian influenza by amantadine. , 1979, JAMA.

[31]  A. Klingner,et al.  Amantadine in Senile Dementia: Electroencephalographic and Clinical Effects , 1979, Journal of the American Geriatrics Society.

[32]  E. Albuquerque,et al.  Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor. , 1978, Science.

[33]  P. Doubilet,et al.  Anticholinergic and membrane activities of amantadine in neuromuscular transmission , 1976, Nature.

[34]  E. Mogilnicka,et al.  Spectrum of pharmacological actions on brain dopamine. Indications for development of new psychoactive drugs. Discussion of amantadines as examples of new drugs with special actions on dopamine systems. , 1976, Polish journal of pharmacology and pharmacy.

[35]  R. Couch,et al.  Antiviral agents in influenza--summary of Influenza Workshop VIII. , 1976, The Journal of infectious diseases.

[36]  C. Marsden,et al.  Psychiatric symptoms during L-dopa therapy for Parkinson's disease and their relationship to physical disability , 1976, Psychological Medicine.

[37]  T. Stone.  RESPONSES OF NEURONES IN THE CEREBRAL CORTEX AND CAUDATE NUCLEUS TO AMANTADINE, AMPHETAMINE AND DOPAMINE , 1976, British journal of pharmacology.

[38]  T. Stone,et al.  The mechanism of action of amantadine in Parkinsonism: a review. , 1975, Archives internationales de pharmacodynamie et de therapie.

[39]  S. Roffler-Tarlov.  Differences between the effects of acute and long-term treatment with desmethylimipramine on reserpine-induced release of amines from rat brain. , 1975, Biochemical pharmacology.

[40]  T. Stone,et al.  Responses of central neurones to amantadine: comparison with dopamine and amphetamine , 1975, Brain Research.

[41]  K. Kadzielawa.  Dopamine receptor in the reward system of the rat. , 1974, Archives internationales de pharmacodynamie et de therapie.

[42]  J. Maj,et al.  Pharmacological effects of 1,3-dimethyl-5-aminoadamantane, a new adamantane derivative. , 1974, European journal of pharmacology.

[43]  J. Davies,et al.  The effect of amantadine, L-dopa, (plus)-amphetamine and apomorphine on the acquisition of the conditioned avoidance response. , 1974, Neuropharmacology.

[44]  G. Cohen,et al.  Evaluation of amantadine as a releasing agent or uptake blocker for H 3 -dopamine in rat brain slices. , 1972, European journal of pharmacology.

[45]  K. E. Moore,et al.  A comparison of the locomotor stimulant properties of amantadine and l- and d-amphetamine in mice. , 1972, Neuropharmacology.

[46]  W. Herblin.  Amantadine and catecholamine uptake. , 1972, Biochemical pharmacology.

[47]  I. Jurna,et al.  Depression by amantadine of drug-induced rigidity in the rat. , 1972, Neuropharmacology.

[48]  U. Ungerstedt,et al.  Dopamine and noradrenaline releasing action of amantadine in the central and peripheral nervous system: a possible mode of action in Parkinson's disease. , 1971, European journal of pharmacology.

[49]  H. Fibiger,et al.  The effect of amantadine on spontaneous locomotor activity in the rat , 1971, The Journal of pharmacy and pharmacology.

[50]  S. Vale,et al.  Amantadine in depression. , 1971, Lancet.

[51]  M. Besson,et al.  Increased synthesis and release of dopamine in the striatum of the rat after amantadine treatment. , 1970, European journal of pharmacology.

[52]  P. Redfern,et al.  The effect of amantadine on the uptake of dopamine and noradrenaline by rat brain homogenates , 1970, The Journal of pharmacy and pharmacology.

[53]  T. Svensson,et al.  Potentiation by amantadine hydrochloride of L‐dopa‐induced effects in mice , 1970, The Journal of pharmacy and pharmacology.

[54]  V. G. Vernier,et al.  Amantadine-Dopamine Interaction: Possible Mode of Action in Parkinsonism , 1970, Science.

[55]  R. Knill-Jones,et al.  Controlled trial of amantadine hydrochloride in Parkinson's disease. , 1970, Lancet.

[56]  V. G. Vernier,et al.  The toxicologic and pharmacologic properties of amantadine hydrochloride. , 1969, Toxicology and applied pharmacology.

[57]  A. Kennedy.  The use of anti-depressive drugs. , 1961, The Journal of mental science.

[58]  R. Balon,et al.  Intermittent amantadine for fluoxetine-induced anorgasmia. , 1996, Journal of sex & marital therapy.

[59]  J. Jaffe,et al.  Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine. , 1992, The International journal of the addictions.

[60]  D. Ziedonis,et al.  Depression as a prognostic factor for pharmacological treatment of cocaine dependence. , 1991, Psychopharmacology bulletin.

[61]  R. Schottenfeld,et al.  Amantadine and desipramine in the treatment of cocaine abusing methadone maintained patients. , 1990, NIDA research monograph.

[62]  A. E. Lang,et al.  Anticholinergic Drugs and Amantadine in the Treatment of Parkinson’s Disease , 1989 .

[63]  F. Tennant,et al.  Double-blind comparison of amantadine and bromocriptine for ambulatory withdrawal from cocaine dependence. , 1987, Archives of internal medicine.

[64]  R. Allen.  Role of Amantadine in the Management of Neuroleptic‐Induced Extrapyramidal Syndromes: Overview and Pharmacology , 1983, Clinical neuropharmacology.

[65]  G. Gianutsos,et al.  Structure-anti-Parkinson activity relationships in the aminoadamantanes. Influence of bridgehead substitution. , 1982, Journal of medicinal chemistry.

[66]  O. Ekenna,et al.  Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of the rat. , 1982, Arzneimittel-Forschung.

[67]  P. Dandiya,et al.  Potentiation of anticatatonic effect of antidepressants by amantadine. , 1977, The Indian journal of medical research.

[68]  R. Papeschi.  Amantadine may stimulate dopamine and noradrenaline receptors. , 1974, Neuropharmacology.

[69]  J. Ananth,et al.  Treatment of intractable depression. , 1974, International pharmacopsychiatry.

[70]  R. Baldessarini,et al.  Effects of amantadine hydrochloride on catecholamine metabolism in the brain of the rat. , 1972, Biochemical pharmacology.

[71]  S. Snyder,et al.  Catecholamine uptake by synaptosomes from rat brain. Structure-activity relationships of drugs with differential effects on dopamine and norepinephrine neurons. , 1971, Molecular pharmacology.

[72]  G. Jackson,et al.  SEROLOGICAL EVIDENCE FOR PREVENTION OF INFLUENZAL INFECTION IN VOLUNTEERS BY AN ANTI-INFLUENZAL DRUG ADAMANTANAMINE HYDROCHLORIDE. , 1963, Antimicrobial agents and chemotherapy.

[73]  L. Stein.  Effects and interactions of imipramine, chlorpromazine, reserpine and amphetamine on self-stimulation: possible neurophysiological basis of depression. , 1961, Recent advances in biological psychiatry.