No abstract

Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.

We investigated the prevalence of anxiety disorders in a sample of individuals with chronic schizophrenia, controlling for anxiety symptoms that may be related to delusions and hallucinations, and the possible differences in clinical variables between the groups. Individuals with a diagnosis of schizophrenia and able to give informed consent were recruited from the community. The Mini International Neuropsychiatric Interview (MINI) was administered to both confirm the DSM-IV diagnosis of schizophrenia and screen for comorbid anxiety disorders. If a comorbid anxiety disorder was found, its relation to the individual's delusions and hallucinations was examined. Clinical rating scales for schizophrenia were administered as well as rating scales for specific anxiety disorders where appropriate. Overall, anxiety disorders ranged from 0% [ for Post Traumatic Stress Disorder (PTSD)] to 26.7% [ for generalized anxiety disorder (GAD) and agoraphobia without panic] with lower rates when controlled for anxiety symptoms related to delusions and hallucinations. In investigating clinical variables, the cohort was initially divided into schizophrenics with no anxiety disorders and those with an anxiety disorder; with further analyses including schizophrenics with anxiety disorders related to delusions and hallucinations and those with anxiety disorders not related to delusions and hallucinations. The most consistent difference between all the groups was on the PANSS-G subscale. No significant differences were found on the remaining clinical variables. Comorbid anxiety disorders in schizophrenia can be related to the individual's delusions and hallucinations, though anxiety disorders can occur exclusive of these positive symptoms. Clinicians must be aware that this comorbidity exists in order to optimize an individual's treatment.