Mechanism of action of ketamine

CNS Spectrums ◽  
2013 ◽  
Vol 18 (4) ◽  
pp. 171-174 ◽  
Author(s):  
Stephen M. Stahl

ISSUE:Ketamine induces rapid-onset and short-duration improvement in depressive and suicidal symptoms in both treatment-resistant unipolar depression and bipolar depression, and also reduces chronic pain after short intravenous infusions. In order to develop long-acting oral agents with the same clinical effects, the pharmacologic mechanism of action must be understood, and the leading hypotheses are discussed here.

CNS Spectrums ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 225-227 ◽  
Author(s):  
Stephen M. Stahl

ISSUE:Reports of rapid-onset but short-duration antidepressant effects in patients with treatment-resistant mood disorders after intravenous administration of ketamine have prompted efforts to find an agent with ketamine's properties that can be administered orally in repeated doses in order to sustain that action. One candidate for this is dextromethorphan, and here the pharmacologic mechanism of action is compared and contrasted with that of ketamine.


CNS Spectrums ◽  
2016 ◽  
Vol 22 (5) ◽  
pp. 391-396 ◽  
Author(s):  
Jonathan M. Meyer ◽  
Michael A. Cummings ◽  
George Proctor

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.


1995 ◽  
Vol 40 (5) ◽  
pp. 270-274 ◽  
Author(s):  
Verinder Sharma ◽  
Dwight Mazmanian ◽  
Emmanuel Persad ◽  
Karen Kueneman

Objective To examine the occurrence of concomitant psychiatric disorders in patients with treatment-resistant unipolar and bipolar depression. Method Forty-nine patients participated as subjects. Twenty-four (49%) had unipolar depression and 25 (51%) had bipolar depression using DSM-III-R criteria. Structured clinical interviews were conducted with all patients. Chart reviews and interviews with family members were also carried out. Information relating to both current and lifetime diagnoses was obtained. Results Of the entire sample, 75.5% were found to have at least one other Axis I diagnosis and 46.9% had at least two additional Axis I diagnoses. The unipolar group had significantly more current comorbid diagnoses. When type of diagnoses was examined, unipolar patients had significantly more anxiety diagnoses at the time of the index episode, and over their entire lifetime. Bipolar patients had significantly more lifetime substance abuse diagnoses. Conclusions Axis I comorbidity appears to be differentially associated with treatment resistance in unipolar and bipolar depression.


2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Nicolas A. Nuñez ◽  
Stefano Comai ◽  
Eduard Dumitrescu ◽  
Maykel F. Ghabrash ◽  
John Tabaka ◽  
...  

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.


Author(s):  
Virginia Carter Leno ◽  
Emily Simonoff

Recent evidence suggests that individuals with autism spectrum disorder (ASD) experience depression at rates approximately four times greater than the general population. Co-occurring mood problems, including depressive and bipolar disorders, are associated with negative outcomes such as lower quality of life, increased adaptive behavior impairments, and greater service use. This chapter discusses what is known about the presentation of unipolar and bipolar depression in people with ASD and describes challenges to establishing sound prevalence estimates of mood disorders in ASD as they relate to methodological design issues and diagnostic assessment practices. It also provides an overview of potential vulnerability factors in the development of depression in this population; these areas of vulnerability include characteristics such as chronological age, cognitive ability, and ASD symptom severity, as well as those individual differences that may represent more direct mechanisms, for example, maladaptive coping styles, attentional biases, social reward profiles, and predisposition to rumination. The current research on interventions specifically designed to treat mood in people with ASD is very limited. However, promising treatments include adapted cognitive behavioral therapy and mindfulness-based approaches. Though most of this chapter focuses on unipolar depression in ASD as the more well-studied mood disorder, the chapter also summarizes the small research base on bipolar disorder in the context of ASD. It ends with a call for improved screening, assessment, and evidence-based treatment options to address this significant public health problem in this special population.


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