Ketamine disorder

Substance-Related Disorders CHAPTER 73 PHENCYCLIDINE AND KETAMINE... 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers. Biol Psychiat 43 811-816. 

Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia. Am J Psychiat 156 1646-1649. 

A placebo-controlled study of low-dose ketamine infusion in ten volunteers showed formal thought disorder and impairments in working and semantic memory (428). The degree of thought disorder correlated with the impairment in working memory. 

PCP binds to a site within the ion channel of the NMDA receptor that blocks the influx of cations, thereby acting as a non-competitive antagonist. PCP produces a syndrome in normal individuals that closely resembles schizophrenia and exacerbates symptoms in patients with chronic schizophrenia. Ketamine is an anesthetic that has approximately a 10- to 15-fold lower affinity for the NMDA receptor, and it produces the characteristic cognitive deficits of schizophrenia. When ketamine is administered to patients with schizophrenia stabilized with antipsychotic medication, it produces delusions, hallucinations, and thought disorder, consistent with the patient s typical pattern of psychotic relapse. Consistent with this model, chronic PCP administration also increases subcortical dopamine release, particularly in the nucleus accumbens, emphasizing the reciprocal modulation of the glutamate and dopamine neuronal systems in schizophrenia. 

Schonenberg M, Reichwald U, Domes G, Badke A, Hautzinger M. Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims. J Psychopharmacol 2008 22(5) 493-7. 

Catalepsy is a feature of many anti-psychotic medications and psychotic disorders. It has been described in animals following the use of ketamine in a dose-dependent fashion but not in the emergency department for procedural sedation. 

A further trial [59 ] investigated e used of repeated doses of ketamine for a mixed group of patients with major depression or bipolar disorder. They used, however, a reduced rate of ketamine infusion to comply with the hospitals monitoring rules (0.5mg/kg at an infusion rate of 0.3mg/kg/hr). Ten patients underwent ketamine infusion... 

Case 1 A 57-year-old female with bipolar disorder and ADHD, previously with multiple failed drug trials had IV ketamine twice weekly. After the third infusion, symptoms were starting to resolve however, relapse occurred at 10 days. IM ketamine (0.5-0.8 mg/ kg) was then administered daily which achieved complete resolution after 2-3 days. After five months there was a partial relapse which was treated by a dose escalation to 70 mg daily. She is currently functional but... 

Case 2 A 48-year-old female with bipolar disorder and ADHD and multiple drug failures. She tried oral ketamine with no effect and then was administered 50 mg intramuscularly every three da). There was improvement in one week and a partial relapse was treated with adjuvant bupropion. S5rmptoms have much improved over a six month period. Mild side effects were observed of headaches and irritability. 

IM ketamine has a much better bioavailability than oral ketamine and therefore may warrant further trials. Psychiatric Post-traumatic Stress Disorder... 

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