Table 5.

Clinical Guideline to Treat Acute Bipolar Depressive Episodes

1st step	• Start with quetiapine, lurasidone, or OFC • Consider add-on CBT. Never consider CBT as monotherapy
2nd step	• Monotherapy with valproate or lithium • Combination of a mood stabilizer with lurasidone, modafinil, or pramipexole • Lithium plus pioglitazone • Carbamazepine plus FEWP • Add escitalopram or fluoxetine on ongoing therapy • For the treatment of comorbid anxiety add paroxetine, quetiapine, valproate, or lurasidone, and consider mindfulness-based interventions as add-on ongoing therapy
3rd step	• Aripiprazole, imipramine, or phenelzine monotherapy • Lithium plus oxcarbazepine or L-sulpiride
4th step	• Olanzapine, lamotrigine, tranylcypromine, or carbamazepine monotherapy • Venlafaxine preferably in combination with an antimanic agent • Armodafinil or ketamine on a mood stabilizer • Lithium plus fluoxetine or lamotrigine
5th step	• ECT • Various combinations of medication according to anecdotal knowledge or the personal experience of the therapist
Not recommended	Monotherapy with donepezil, paroxetine (except for comorbid anxiety), ziprasidone, gabapentin, lithium and rTMS, combination of any mood stabilizer with agomelatine, paroxetine, ziprasidone, bupropion, celecoxib, levetiracetam, lisdexamfetamine or risperidone, Memantine plus lamotrigine and lithium plus aripiprazole, donepezil or imipramine. Not recommended also risperidone or ziprasidone for the treatment of concomitant anxiety

Abbreviations: CBT, cognitive behavioral treatment; Cbz, carbamazepine; ECT, electroconvulsive therapy; FEWP, Free and Easy Wanderer Plus; IPSRT, interpersonal and social rhythms therapy; Lam, lamotrigine; MS, mood stabilizer; OFC, olanzapine fluoxetine combination; rTMS, repetitive Transcranial Magnetic Stimulation; Val, valproate.