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Ketamine

The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report

February 6, 2015 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , ,

Abstract

In contrast to improvement in emotion recognition bias by traditional antidepressants, the authors report preliminary findings that changes in facial emotion recognition are not associated with response of depressive symptoms after repeated ketamine infusions or relapse during follow-up in treatment-resistant depression.

Shiroma, P. R., Albott, C. S., Johns, B., Thuras, P., Wels, J., & Lim, K. O. (2015). The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report. The Journal of Neuropsychiatry and Clinical Neurosciences. http://dx.doi.org/10.1176/appi.neuropsych.14100243
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Drug models of schizophrenia

February 5, 2015 / Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.

Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology. https://dx.doi.org/10.1177/2045125314557797
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Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia

February 1, 2015 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

Objective

Studies of the effects of the N-methyl-d–aspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages).

Method

We conducted exploratory factor analysis for the PANSS from four groups: 135 healthy subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154 inpatients of early course schizophrenia and 522 inpatients of chronic schizophrenia. Principal component factor analyses were conducted to identify the factor structure of the PANSS.

Results

Factor analysis yielded five factors for each group: positive, negative, cognitive, depressed, excitement or dissociation symptoms. The symptom dimensions in two schizophrenia groups were consistent with the established five-factor model (Wallwork et al., 2012). The factor structures across four groups were similar, with 19 of 30 symptoms loading on the same factor in at least 3 of 4 groups. The factors in the chronic ketamine group were more similar to the factors in the two schizophrenia groups rather than to the factors in the acute ketamine group. Symptom severities were significantly different across the groups (Kruskal–Wallis χ2(4) = 540.6, p < 0.0001). Symptoms in the two ketamine groups were milder than in the two schizophrenia groups (Cohen’s d = 0.7).

Conclusion

Our results provide the evidence of similarity in symptom dimensions between ketamine psychosis and schizophrenia psychosis. The interpretations should be cautious because of potential confounding factors.

Xu, K., Krystal, J. H., Ning, Y., He, H., Wang, D., Ke, X., … & Fan, N. (2015). Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal of psychiatric research, 61, 64-72. https://dx.doi.org/doi:10.1016/j.jpsychires.2014.12.012
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Antidepressant actions of ketamine: from molecular mechanisms to clinical practice

February 1, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants.

Monteggia, L. M., & Zarate, C. (2015). Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Current opinion in neurobiology, 30, 139-143. https://dx.doi.org/doi:10.1016/j.conb.2014.12.004
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Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival

January 28, 2015 / Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof’s psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population’s views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (p<.05) confirming crisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor’s profile and vulnerability to crisis showed inconclusive.

Carvalho, M. C., de Sousa, M. P., Frango, P., Dias, P., Carvalho, J., Rodrigues, M., & Rodrigues, T. (2015). Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings-Evaluating the Kosmicare Project at Boom Festival. Current Drug Abuse Reviews, 7(2), 81-100. https://dx.doi.org/10.2174/1874473708666150107115515

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Can psychedelic compounds play a part in drug dependence therapy?

January 5, 2015 / Ayahuasca, Iboga / Ibogaine, Ketamine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.

Sessa, B., & Johnson, M. W. (2015). Can psychedelic compounds play a part in drug dependence therapy? The British Journal of Psychiatry, 206, 1-3. https://dx.doi.org/10.1192/bjp.bp.114.148031

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Ketamine interactions with biomarkers of stress: A randomized placebo-controlled repeated measures resting-state fMRI and PCASL pilot study in healthy men

December 29, 2014 / Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Ketamine, an NMDA receptor antagonist, is increasingly used to study the link between glutamatergic signaling dysregulation and mood and chronic pain disorders. Glutamatergic neurotransmission and stress corticosteroids (cortisol in human) are critical for Ca2 + mediated neuroplasticity and behavioral adaptation. The mechanisms of action of glutamatergic neurotransmission and stress corticosteroids on the NMDA-receptors of the hippocampus have been long studied in animals, but given little attention in human studies. In this randomized single-blinded placebo-controlled crossover study (12 healthy young men), five sets of resting-state fMRI (RSFMRI), pseudocontinuous arterial spin labeling (PCASL), and corresponding salivary cortisol samples were acquired over 4 h, at given intervals under pharmacokinetically-controlled infusion of subanesthetic ketamine (20 & 40 mg/70 kg/h). An identical procedure was repeated under a sham placebo condition. Differences in the profile of ketamine versus placebo effect over time were examined. Compared to placebo, ketamine mimicked a stress-like response (increased cortisol, reduced calmness and alertness, and impaired working memory). Ketamine effects on the brain included a transient prefrontal hyperperfusion and a dose-related reduction of relative hippocampal perfusion, plus emerging hyperconnectivity between the hippocampus and the occipital, cingulate, precuneal, cerebellar and basal ganglia regions. The spatiotemporal profiles of ketamine effects on different hippocampal subnetworks suggest a topographically dissociable change in corticohippocampal functional connectivity. We discuss our findings in the context of the negative feedback inhibition theory of the hippocampal stress control. This pilot study provides a methodological framework for multimodal functional neuroimaging under resting-state conditions, which may be generalized for translational studies of glutamatergic- or stress-related etiology of neuropsychiatric disorders.

Mahani, N. K., Niesters, M., van Osch, M. J., Oitzl, M., Veer, I., de Rooij, M., … & Dahan, A. (2014). Ketamine Interactions with Biomarkers of Stress: A randomized placebo-controlled repeated measures resting-state fMRI and PCASL pilot study in healthy men. NeuroImage. https://dx.doi.org/10.1016/j.neuroimage.2014.12.050
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Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

December 26, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Summary

What is known and objective

The current pharmacotherapeutic treatment of major depressive disorder (MDD) generally takes weeks to be effective. As the molecular action of these drugs is immediate, the mechanistic basis for this lag is unclear. A drug that has a more rapid onset of action would be a major therapeutic advance and also be a useful comparator to provide valuable mechanistic insight into the disorder and its treatment.

Comment

Recent evidence suggests that ketamine produces rapid-onset antidepressant action. Important questions are as follows: is it specific or coincidental to other effects; is there a dose–response relationship; and is the mechanism related to that of current antidepressants. NMDA receptor antagonism is unlikely the explanation for ketamine’s antidepressant action.

What is new and conclusion

It is not an exaggeration to state that the new findings, if validated, might produce a revolution in understanding and treating depressive disorders.

Drewniany, E., Han, J., Hancock, C., Jones, R. L., Lim, J., Nemat Gorgani, N., … & Raffa, R. B. (2014). Rapid‐onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression. Journal of Clinical Pharmacy and Therapeutics. https://dx.doi.org/10.1111/jcpt.12238
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Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

December 17, 2014 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.

Murrough, J. W., Burdick, K. E., Levitch, C. F., Perez, A. M., Brallier, J. W., Chang, L. C., … & Iosifescu, D. V. (2014). Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial. Neuropsychopharmacology. https://dx.doi.org/10.1038/npp.2014.298

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A single infusion of ketamine improves depression scores in patients with anxious bipolar depression

November 14, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Objective

Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine’s ability to decrease symptoms of depression.

Methods

Thirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7.

Results

A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28).

Conclusions

Both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.

Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Richards, E. M., & Zarate, C. A. (2014). A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar disorders. https://dx.doi.org/10.1111/bdi.12277

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