Bipolar disorder type 1 is a serious chronic psychiatric condition often featuring refractory depressive episodes. Racemic ketamine, a glutamate modulator with dissociative and psychedelic properties, has demonstrated rapid antidepressant and anti-obsessional effects that may help treat bipolar depression. Existing research has mostly examined sub-psychedelic doses given by infusion without psychotherapy. This article expands on that work by describing three paradigms for ketamine treatment: biochemical, psychotherapeutic, and psychedelic. The authors use composite clinical vignettes to illustrate different ways of using ketamine for bipolar depression and discuss clinical considerations including route, dose, frequency, chemical mitigators, and adverse events. The paradigms have broad applicability beyond bipolar treatment.
Rapid acting antidepressants (RAADs), including ketamine and its derivatives along with GABA receptor modulators, can produce mood improvements within hours or days rather than weeks. There is also renewed interest in psychedelic compounds affecting multiple receptor sites. However, the rating instruments used to measure antidepressant response, such as the Hamilton and Montgomery-Åsberg depression rating scales, were designed decades ago for older drugs and assess symptoms over a seven-day timeframe. This review describes adaptations made to these existing scales for use with RAADs, including modifications for items like sleep and appetite that cannot be assessed in short time frames, and examines additional domains such as daily activities, side effects, suicidal ideation, and role functioning. Recommendations for future studies and implementation challenges are discussed.