Depression represents the predominant mood pole in bipolar disorder. Bipolar depression typically has a poor response to antidepressant medication, and also involves the risk of polarity shifts, induction of mixed states, and / or rapid cycle induction. The diagnosis of bipolar depression can be delayed by 8 to 10 years. The reason for this delay is mainly the fact that both manic and hypomanic episodes appear lately in the course of the disorder. It is therefore necessary to diagnose this clinical entity as early as possible versus monopolar depression in order to treat it more effectively. This differential diagnosis is based on certain clinical features of bipolar depression, which are often difficult to be distinguished from those of monopolar depression and therefore it is necessary to know specific criteria that differentiate them to some extent qualitatively and / or quantitatively. Such characteristics are daily mood swings, multiple physical complaints, psychomotor retardation, psychotic elements (delusions and perceptual disorders mood congruent or noncongruent), the disturbance of certain bodily functions, including circadian rhythms, sexual desire, appetite, and disorders of sleep architecture. The treatment of bipolar depression is based on the options known from monopolar depression (such as the use of antidepressants, antipsychotics, and certain antiepileptic agents) and their combinations, while in recent years it has been enriched with new pharmaceutical agents and non-pharmacological approaches. New glutaminergic regulators dominate the new pharmacological agents’ research, and among them the antidepressant effect of ketamine and esketamine at sub-anesthetic doses is being extensively investigated during recent years. Non-pharmacological approaches include methods such as electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS), sleep deprivation, and phototherapy.

ΚΕΥWORDS: Bipolar depression, clinical presentation, differential diagnosis, pharmaceutical therapy, non- pharmaceutical therapies.

Grigorios N. Karakatsoulis, Eva-Maria Tsapakis, Konstantinos N. Fountoulakis


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