Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacological reports: PR (Impact Factor: 1.93). 01/2007; 59(6):778-84.
Source: PubMed

ABSTRACT The paper describes the effect of amantadine addition to imipramine therapy in patients suffering from treatment-resistant unipolar depression who fulfilled DSM IV criteria for major (unipolar) depression. Fifty patients were enrolled in the study on the basis of their histories of illness and therapy. After a 2-week drug-free period, 25 subjects belonging to the first group were treated only with imipramine twice daily (100 mg/day) for 12 weeks, and 25 subjects belonging to the second group were treated with imipramine twice daily (100 mg/day) for 6 weeks and then amantadine was introduced (150 mg/day, twice daily) and administered jointly with imipramine for the successive 6 weeks. Hamilton Depression Rating Scale (HDRS) was used to assess the efficacy of antidepressant therapy. Imipramine did not change the HDRS score after 3, 6 or 12 weeks of treatment when compared with the washout (before treatment). The addition of amantadine to the classic antidepressant reduced HDRS scores after 6-week joint treatment. Moreover, the obtained pharmacokinetic data indicated that amantadine did not significantly influence the plasma concentration of imipramine and its metabolite desipramine in patients treated jointly with imipramine and amantadine, which suggests lack of a pharmacokinetic interaction. The obtained results indicate that joint therapy with an antidepressant and amantadine may be effective in treatment-resistant unipolar depression.

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Available from: Grażyna Skuza, Oct 16, 2014
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    • "Since not all patients respond to ketamine, its efficacy as well as safety profile need further confirmation [11] [12] [13] [14]. As reported by clinicians, other non-specific NMDA receptor antagonists like amantadine potentiated the effects of conventional antidepressant therapy in not responding disease [15] [16], while zinc, an inorganic modulator of the NMDA receptor complex, augmented the efficacy of drugs given to patients with major depression [17] [18]. Amongst more promising, devoid of the unwanted effects agents acting at the NMDA receptor sites, ifenprodil also should be mentioned. "
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    ABSTRACT: Background According to reports in the literature, more than 30% of depressive patients fail to achieve remission. Therapy with the conventional antidepressant drugs may induce the serious adverse reactions. Moreover, its benefits may be seen at least 2–4 weeks after the first dose. Therefore, the alternative strategies for prevention and treatment of depression are sought. The main aim of our study was to assess the effects of ifenprodil given at a non-active dose (10 mg/kg) on the activity of antidepressant agents from diverse pharmacological groups. Methods The antidepressant-like effect was assessed by the forced swim test in mice. Results Ifenprodil potentiated the antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (5 mg/kg) while did not reduce the immobility time of animals which simultaneously received reboxetine (2.5 mg/kg) or tianeptine (15 mg/kg). Conclusion The concomitant administration of certain commonly prescribed antidepressant drugs that affect the serotonergic neurotransmission (i.e., typical tricyclic antidepressants and selective serotonin reuptake inhibitors) with a negative modulator selectively binding to the GluN1/N2B subunits of the NMDA receptor complex (i.e., ifenprodil) may induce a more pronounced antidepressant-like effect than monotherapy. However, these findings still need to be confirmed in further experiments.
    Pharmacological reports: PR 12/2014; 66(6):1031–1036. DOI:10.1016/j.pharep.2014.06.016 · 1.93 Impact Factor
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    • "Besides, the anti-depressive function of the NMDA receptor antagonist has been noted in recent studies [22] [23]. In particular, amantadine has shown a mild anti-depressive effect when used alone, but has proved an effective adjunctive treatment when combined with other anti-depressants in both human and animal models [24]. "
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    ABSTRACT: Traumatic brain injury (TBI) often results in multiple neuropsychiatric sequelae, including cognitive, emotional, and behavioral problems. Among them, depression is a common psychiatric symptom, and links to poorer recovery. Amantadine, as an antiparkinsonian, increases dopamine release, and blocks dopamine reuptake, but has recently received attention for its effectiveness as an antidepressant. In the present study, we first induced a post-TBI depression rat model to probe the efficacy of amantadine therapy in reducing post-TBI depression. The DA concentration in the striatum of the injured rats, as well as the degeneration and apoptosis of dopaminergic neurons in the substantia nigra (SN), were checked along with the depression-like behavior. The results showed that amantadine therapy could significantly ameliorate the depression-like behavior, improving the DA level in the striatum and decreasing the degeneration and apoptosis of dopaminergic neurons in the SN. The results indicated that the anti-depression effect may result from the increase of extracellular DA concentration in the striatum and/or the indirect neuroprotection on the dopaminergic neurons in the SN. We conclude that DA plays a critical role in post-TBI depression, and that amantadine shows its potential value in anti-depression treatment for TBI. Copyright © 2014. Published by Elsevier B.V.
    Behavioural Brain Research 11/2014; 279. DOI:10.1016/j.bbr.2014.10.037 · 3.03 Impact Factor
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    • "Compared with the other antiparkinsonian drugs, amantadine displays fewer adverse effects (Danielczyk, 1995), while Merims and colleagues claimed that amantadine causes no hallucinations in PD patients (Merims et al., 2004). Apart from PD, amantadine may be beneficial in other neurological conditions such as brain trauma (Leone and Polsonetti, 2005) and depression (Rogoz et al., 2007). "
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    ABSTRACT: Amantadine is commonly given to alleviate L-DOPA-induced dyskinesia of Parkinson's disease (PD) patients. Animal and human evidence showed that amantadine may also exert neuroprotection in several neurological disorders. Additionally, it is generally believed that this neuroprotection results from the ability of amantadine to inhibit glutamatergic NMDA receptor. However, several lines of evidence questioned the neuroprotective capacity of NMDA receptor antagonists in animal models of PD. Thus the cellular and molecular mechanism of neuroprotection of amantadine remains unclear. Using primary cultures with different composition of neurons, microglia, and astroglia we investigated the direct role of these glial cell types in the neuroprotective effect of amantadine. First, amantadine protected rat midbrain cultures from either MPP(+) or lipopolysaccharide (LPS), two toxins commonly used as PD models. Second, our studies revealed that amantadine reduced both LPS- and MPP(+)-induced toxicity of dopamine neurons through 1) the inhibition of the release of microglial pro-inflammatory factors, 2) an increase in expression of neurotrophic factors such as GDNF from astroglia. Lastly, differently from the general view on amantadine's action, we provided evidence suggesting that NMDA receptor inhibition was not crucial for the neuroprotective effect of amantadine. In conclusion, we report that amantadine protected dopamine neurons in two PD models through a novel dual mechanism, namely reducing the release of pro-inflammatory factors from activated microglia and increasing the expression of GNDF in astroglia.
    Neuropharmacology 05/2011; 61(4):574-82. DOI:10.1016/j.neuropharm.2011.04.030 · 5.11 Impact Factor
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