Ketamine, antidepressants and online CBT did not change goal-directed planning in depression

The question

Does a person’s ability to plan ahead in a goal-directed way (‘model-based planning’) improve when their depression is treated with ketamine, antidepressant medication or internet-based cognitive behavioural therapy?

What they did

Two parallel studies asked people to do a two-step computer learning task before and after treatment. In the first, 93 people with treatment-resistant depression were randomly assigned to a single intravenous dose of ketamine (0.5 mg/kg) or an intravenous saline placebo (50 mL 0.9% NaCl). In the second, 781 people were followed for four weeks of antidepressant medication (83 people) or internet-based cognitive behavioural therapy (611 people), alongside 87 people with no psychiatric diagnosis as a comparison group.

What they found

Depressive symptoms improved significantly in the treatment groups compared with their control groups. Despite this, the researchers found no evidence that model-based planning changed after any of the three treatments. They also found no link between a person’s baseline planning ability and how well they responded to ketamine, online CBT or antidepressants. Baseline differences in planning were associated with compulsivity, but not with depression symptoms.

The fine print

This is a null result, and absence of evidence for change is not proof that no change exists. Follow-up was short (four weeks in the second study, and a single ketamine dose in the first), so longer-term effects were not tested. Only the ketamine comparison was randomized and placebo-controlled; the antidepressant and online CBT groups were not randomized against each other, and group sizes were very uneven. This summary is based on the abstract alone.

What it means

Treatments that reduced depressive symptoms did not appear to shift this particular measure of goal-directed planning, suggesting the ability may be a stable trait rather than something depression disrupts and treatment restores.

Evidence grade: Moderate. One randomized placebo-controlled ketamine trial combined with a large but non-randomized observational follow-up of other treatments, with a short four-week window and a cognitive task rather than a clinical outcome as the main measure.

This summary is based on the study’s published abstract.