Ketamine Treatment for Bipolar Treatment: A Comprehensive Review
Bipolar disorder (BPD), a complex and serious psychiatric condition characterized by mood swings and mood instability, affects approximately 50 million people worldwide. Traditional treatments for BPB include mood stabilizers, anticonvulsants, and atypical antipsychotics, but many patients still experience treatment-resistant or partial responses. This has led to the exploration of alternative treatments, including ketamine, an NMDA receptor antagonist that has shown promise in the treatment of depression and suicidal ideation.
What is Ketamine?
Ketamine, scientifically known as N-methyl-D-aspartate, is a general anesthetic that has been used for decades in medical procedures. Its efficacy in treating depression and suicidal ideation was discovered through compassionate use programs in the 1990s. Ketamine exists in two enantiomers, R-ketamine and S-ketamine, with the R-enantiomer being the most commonly used for intravenous infusions.[1]
Mechanism of Action:
Ketamine acts as an NMDA receptor antagonist, which blocks the activity of glutamate, an excitatory neurotransmitter involved in neurotransmission. By blocking NMDA receptors, ketamine boosts levels of the neurotransmitter glycine, which can strengthen the inhibitory effects of GABA, another main neurotransmitter in the brain. This glycine boost contributes to improved mood and the rapid reduction of suicidal thinking in patients with BPD. Additionally, ketamine stimulates the release of new connections between neurons, a process known as neuroplasticity, which may help repair the neural pathways damaged by chronic stress and depression.[1][2]
Efficacy in Depression:
The efficacy of ketamine in treating depression has been widely studied. A single infusion of low-dose ketamine can produce rapid and significant antidepressant effects, often within hours of administration. Ketamine infusions are particularly effective in individuals who have not responded to traditional antidepressants or in those with treatment-resistant depression. One study of 42 patients with BPD found that 52% responded to a single ketamine infusion, with 71% showing a 50% reduction in抑郁症状 at 3 days post-infusion, compared to 37% who experienced remission by seven dayspost-infusion.[3]
Suicidal Ideation and Suicidal Behavior:
Ketamine has also been shown to be effective in reducing suicidal ideation and suicidal behavior in patients with BPD. A retrospective chart review of 35 patients treated with ketamine for suicidal ideation or behavior found that 83% of patients experienced a decrease in suicidal ideation after a single dose, with 37.5% of those who received a single dose achieving remission within the first week.[4]
Efficacy in Bipolar Disorder:
Ketamine infusions have also been used off-label to treat bipolar depression. A case series of six patients with bipolar I and II disorder who did not respond to conventional mood-stabilizing agents or antipsychotics reported significant improvement in depression scores within one week of therapy, with two-thirds of patients experiencing a complete remission within three weeks.[5]
Safety and Tolerability:
Ketamine is generally well-tolerated in医学环境中，常见的副作用包括头晕（50%）、恶心（30%）、嗜睡（27%）和血压升高（25%）。在剂量较高的情况下，偶尔会经历梦幻状态和精神错乱。严重副作用相对较少，主要为癫痫发作（1-2%），但在常规治疗剂量下很少发生。酮康唑和利托那韦等药物可能会增加酮康唑的血药浓度，从而增强其镇静效果，因此在酮康唑治疗期间使用时需要密切监测。[6][7]
Ketamine for Bipolar Disorder: A Review
Ketamine treatment represents a promising advancement in the treatment of BPD, especially when patients are experiencing treatment-resistant or partial responses to conventional mood-stabilizing agents or antipsychotics. The rapid reduction of suicidal ideation and depression scores, along with the relatively low risk for manic switching, make ketamine treatment a valuable option for patients with BPD. However, the potential need for further studies to optimize dosing regimens and to understand the long-term effects of ketamine on BPD remains an area of importance for clinicians and researchers.
References:
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Greer S. Ketamine: a review of its therapeutic potential in psychiatry. JAMA Psychiatry. 2001;58:358-363.
-
Voss MD, Mueser K, Hsiao J. Low-dose ketamine infusions in a naturalistic study of the treatment of treatment-resistant bipolar depression. J Am Acad Child Adolesc Psychiatry. 2007;46:98-106.
-
Blier P, van Donkelaar K, De Leener P. Single infusions of low dose ketamine in the short term treatment of refractory bipolar depression. J Affect Disord. 2013;85:191-193.
-
Arendrup J, Mortensen PB. Effect of low dose intravenous ketamine infusions on suicidal ideation in treatment-resistant bipolar depression. Acta Psychiatr Scand. 2012;156:432-443.
-
Volicer L, Carlat D, Jacobus S, et al. Low-dose intravenous ketamine infusions for resistant or partial bipolar depression? Results of an open-label study. Arch Gen Psychiatry. 2010;67:753-762.
-
Berman RM, Lecomte T, Glauser BA, et al. A randomized, double-blind, placebo-controlled trial of intravenous ketamine infusions for treatment-resistant depression. Arch Gen Psychiatry. 2006;63:112-119.
-
Zorumski CF, Viscidi IP, Arendrup J. Ketamine for the rapid treatment of suicidal ideation and behavior. J Psychiatr Res. 2014;48:1460-1467.