OPEN Foundation

T. Vanicek

Administration of ketamine for unipolar and bipolar depression

Abstract

OBJECTIVE: Clinical trials demonstrated that ketamine exhibits rapid antidepressant efficacy when administered in subanaesthetic dosages. We reviewed currently available literature investigating efficacy, response rates and safety profile.

METHODS: Twelve studies investigating unipolar, seven on bipolar depression were included after search in medline, scopus and web of science.

RESULTS: Randomized, placebo-controlled or open-label trials reported antidepressant response rates after 24 h on primary outcome measures at 61%. The average reduction of Hamilton Depression Rating Scale (HAM-D) was 10.9 points, Beck Depression Inventory (BDI) 15.7 points and Montgomery-Asberg Depression Rating Scale (MADRS) 20.8 points. Ketamine was always superior to placebo. Most common side effects were dizziness, blurred vision, restlessness, nausea/vomiting and headache, which were all reversible. Relapse rates ranged between 60% and 92%. To provide best practice-based information to patients, a consent-form for application and modification in local language is included.

CONCLUSIONS: Ketamine constitutes a novel, rapid and efficacious treatment option for patients suffering from treatment resistant depression and exhibits rapid and significant anti-suicidal effects. New administration routes might serve as alternative to intravenous regimes for potential usage in outpatient settings. However, long-term side effects are not known and short duration of antidepressant response need ways to prolong ketamine’s efficacy.

Kraus, C., Rabl, U., Vanicek, T., Carlberg, L., Popovic, A., Spies, M., … & Willeit, M. (2017). Administration of ketamine for unipolar and bipolar depression. International Journal of Psychiatry in Clinical Practice, 21(1), 2-12. 10.1080/13651501.2016.1254802
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Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

Abstract

BACKGROUND:

Schizophrenia has been associated with disturbances of thalamic functioning. In the light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether the modulation of the glutamatergic system via blockage of the NMDA-receptor might lead to changes of thalamic functional connectivity.

METHODS:

Based on the “ketamine-model” of psychosis we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55 minutes resting-state scan. 30 healthy volunteers were measured with pharmacological functional magnetic resonance imaging (fMRI) using a double-blind, randomized, placebo-controlled, crossover design.

RESULTS:

Functional connectivity analysis revealed significant ketamine-specific changes within the “thalamus hub network”, more precisely an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.

CONCLUSIONS:

Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behaviour during the application of NMDA-receptor antagonists.

Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., … & Guertel, W. (2015). Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. The international journal of neuropsychopharmacology. http://dx.doi.org/10.1093/ijnp/pyv040
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