Depression and alcohol use disorder (AUD) often coexist and can create significant
challenges for individuals seeking effective treatment. Traditional treatment approaches
have shown limited success in addressing both conditions simultaneously. Ketamine has
shown to have promising rapid antidepressant effects and a possible role in the treatment
of substance use disorders. By targeting both depression and AUD simultaneously, ketamine
has the potential to offer dual benefits, improving depressive symptoms while addressing
alcohol cravings or consumption. Furthermore, rapid relief from depressive symptoms may
enhance motivation for recovery, reduce the risk of relapse, and improve overall
treatment engagement and outcomes. Although ketamine is generally considered safe when
administered under medical supervision, the safety profile in individuals with comorbid
depression and AUD needs further investigation. The overall objective of this study is to
examine the safety and efficacy of ketamine on adults with depression and AUD that are
admitted for standard inpatient addiction therapy.
The study will only include adults with at least moderate depression and alcohol use
disorder as their primary substance use disorder that are admitted for inpatient
addiction therapy. Participants that are unable to give informed consent or have
contraindication(s) for ketamine will be excluded.
After screening and enrollment, participants will undergo baseline assessments with
measures on depression (using Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck
Depression Inventory-II (BDI-II)), alcohol use (using Timeline Follow-Back method
(TLFB)), alcohol craving (using Short version of Alcohol Craving Questionnaire
(ACQ-Short) and Penn Alcohol Craving Scale (PACS)) and neurocognitive function (using
Cambridge Neuropsychological Test Automated Battery (CANTAB)). Participants will then be
randomized to intervention group or control group. The intervention group will receive
ketamine as four single doses, given biweekly for two weeks. The control group will
receive midazolam as active placebo. Participants will undergo several follow-up
assessments after treatment (1-2 day(s), 1 week, 2 weeks and 4 weeks after treatment).
Final follow-up assessment will be 6 months after baseline.
By using open questions and specific instruments for assessing adverse effects associated
with ketamine (using modified version of Ketamine Side Effect Tool (mKSET)), the trial
will assess the frequency, severity and duration of any adverse events and severe adverse
events. All adverse events will be evaluated with regards to its causal relationship to
ketamine. In addition, physician-assessed and patient-assessed tolerability will be
registered. Changes in neurocognitive function from baseline will be assessed after
treatment.
Changes in depression will be measured several times using rater-blinded MADRS-assessment
and self-report instrument (BDI-II). Measures of alcohol use (TLFB), alcohol craving
(ACQ-short and PACS), relapse risk and time until relapse will used as measures on
alcohol use disorder following treatment. Several exploratory objectives will be
examined, including changes in alcohol dependence severity (using Severity of Alcohol
Dependence Questionnaire (SADQ)), changes in quality of life (using World Health
Organizations brief quality of life questionnaire (WHOQOL-BREF)), changes in
self-reported treatment effectiveness (using Treatment Effectiveness Assessment (TEA))
and changes in anxiety (using Generalized Anxiety Disorder scale (GAD-7)). Finally, data
on the subjective experience of the treatment (using Ego Dissolution Inventory (EDI),
Emotional Breakthrough Inventory (EBI) and Mystical Experience Questionnaire (MEQ30))
will be collected and used in a regression model with baseline measures to assess
predictors of treatment response on measures of depression and AUD .