Treatment of Bipolar Depression

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

Lithium, lamotrigine, and olanzapine-fluoxetine combination therapy are first-line treatments for bipolar depression. The response 

Some patients with bipolar disorder will need antidepressants. Although the switch rate into mania or induction of rapid cychng by antidepressants is controversial, these agents do appear to present a risk for some patients, often with devastating consequences. Therefore, when a patient with bipolar disorder is prescribed an antidepressant, it should only be in combination with a medication that has established antimanic properties. Controlled comparative data on the use of specific antidepressant drugs in the treatment of bipolar depression are sparse. Current treatment guidelines extrapolate from these few studies and rely heavily on anecdotal chnical experience. Overah, tricyclic antidepressants should be avoided when other viable treatment options exist. Electroconvulsive therapy should be considered in severe cases. 

---

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E and Moller H-J (2002). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of bipolar disorders. Part 1 Treatment of bipolar depression. World Journal of Biological Psychiatry, 3, 115-124. 

Bowden, C.L., Mitchell, P., and Suppes, T. (1999) Lamotrigine in the treatment of bipolar depression. Eur Neuropsychopharmacol 9 (Suppl 4) S113-S117. 

In contrast with lithium, there are no controlled trials of valproate in the treatment of bipolar depression. Three uncontrolled reports (Hayes 1989 ... 

Deicken RF Verapamil treatment of bipolar depression (letter). J Chn Psycho-pharmacol 10 148-149, 1990... 

Hussain M, Chaudhry Z. Treatment of bipolar depression with topiramate [Abstract]. Presented at the XI World Congress of Psychiatry, Hamburg, Germany, August 6-11,1999 [free communication] 41-45, 58. 

Closely related to imipramine and other antidepressants, carbamazepine is a tricyclic compound effective in treatment of bipolar depression. It was initially marketed for the treatment of trigeminal neuralgia but has proved useful for epilepsy as well. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Clozapine has well-documented efficacy in the treatment of mania, including treatment-resistant mania [74], although it has not been approved for this indication. Olanzapine and quetiapine both have been approved for the treatment of mania, though not for the treatment of bipolar depression. Olanzapine also has approval for maintenance treatment of bipolar disorder. 

Post, R., Leverich G., Nolen, W., Kupka, R., Altshuler, L., Frye, M., et al. (2003). A re-evaluation of the role of antidepressants in the treatment of bipolar depression Data from the Stanley Foundation Bipolar Network. Bipolar Disorders, 5, 396—406. 

Lamotrigine is approved for the treatment of bipolar depression. This anticonvulsant has been shown to have antidepressant properties that are apparently unique among other anticonvulsants currently used for the treatment of bipolar disorder. Although lamotrigine s antimanic properties may be modest, because of its contribution to the often difficult-to-treat bipolar depressive episodes, we are likely to see its use increase. 

Lamotragine has been shown to be effective in the treatment of bipolar depression. It does not cause weight gain (Bowden et al. 2004). 

Sachs GS, Koslow CL, Ghaemi SN. The treatment of bipolar depression. Bipolar Disord 2000 2 256-260. 

Keck PE Jr., Nelson EB, McElroy SL. Advances in the pharmacologic treatment of bipolar depression. Biol Psychiatry 2003 53 671—... 

Lamotrigine seems to be more effective than iithium in such cases, especially taking into consideration the proven greater efficacy of iamotrigine in the treatment of bipolar depression.Carhamazepine, an anticonvulsant with known mood-stabilizing capacity, also seems to be superior to lithium in schizoaffective disorder, depressed type, and it may also be used in subsequent prophylaxis. 

Lithium is used for the treatment of bipolar depression and other psychiatric disorders and occasionally to boost the white blood cell count in patients with leukopenia. Serious toxicity is most commonly caused by chronic ovennedication in patients with renal impainnent. Acute overdose, in contrast, is generally less severe. 

A systematic review and meta-analysis of second-generation antipsychotics (SGAs) in the treatment of bipolar depression found considerable clinical and statistical heterogeneity of the data with a preponderance of quetiapine studies (9) compared to olanzapine (1) and aripiprazole (2) [22 ]. Adverse events were defined differently and... 

De Fruyt J, Deschepper E, Audenaert K, Constant E, Boris M, Pitchot W, et al. Second generation antipsychotics in the treatment of bipolar depression systematic review and meta-analysis. J Psychopharmacol 2012 26(5) 603-17. 

Gao K, Pappadopulos E, Karayal ON, Kolluri S, Calabrese JR. Risk for adverse events and discontinuation due to adverse events of zipra-sidone monotherapy relative to placebo in the acute treatment of bipolar depression, mania, and schizophrenia. J Clin Psychopharmacol 2013 33(3) 425 1. 

---