BIPOLAR DISORDER: WHY LITHIUM IS STILL FIRST CHOICE
- Posted by Alan Eppel
- Posted in Review Articles
Nervenarzt. 2014 Sep;85(9):1166-70. doi: 10.1007/s00115-014-4083-x.
[New facts of long-term prophylaxis for bipolar affective disorder].
[Article in German]
Bschor T1, Müller-Oerlinghausen B, Stoppe G, Hiemke C.
Lithium and with restrictions, carbamazepine, valproic acid, lamotrigine, olanzapine, aripiprazole and quetiapine, are approved in Germany for maintenance treatment of bipolar disorder.
Lithium is the only drug that (I) proved to be effective for the prevention of depressive as well as manic episodes in state-of-the-art studies without an enriched design and that (II) is approved for the maintenance treatment of bipolar disorders without restrictions. It (III) is also the only drug which is recommended for maintenance treatment by the current German S3 guidelines on bipolar disorders with the highest degree of recommendation (A) and (IV) is the only drug with a well proven suicide preventive effect. Hence, lithium is the mood stabilizer of first choice.
No patient should be deprived of lithium without a specific reason. Side effects and risks are manageable if both the physician and the patient are well informed.
For patients who do not respond sufficiently to lithium, have contraindications or non-tolerable side effects, other mood stabilizers should be used. Restrictions in their respective approval as well as specific side effects and risks have to be taken into account.
Because maintenance treatment is a long-term treatment, particular concern should be paid to drugs with the potential risk of a metabolic syndrome, particularly atypical antipsychotics.
Harv Rev Psychiatry. 2014 Nov-Dec;22(6):353-7. Factors associated
with lithium efficacy in bipolar disorder.
About one-third of lithium-treated, bipolar patients are excellent lithium responders; that is, lithium monotherapy totally prevents further episodes of bipolar disorder for ten years and more. These patients are clinically characterized by an episodic clinical course with complete remission, a bipolar family history, low psychiatric comorbidity, mania-depression episode sequences, a moderate number of episodes, and a low number of hospitalizations in the pre-lithium period.
Recently, it has been found that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis.
Lithium exerts a neuroprotective effect, in which increased expression of brain-derived neurotrophic factor (BDNF) and inhibition of the glycogen synthase kinase-3 (GSK-3) play an important role. The response to lithium has been connected with the genotype of the BDNF gene and serum BDNF levels. A better response to lithium is connected with the Met allele of the BDNF Val/Met polymorphism, as is a hyperthymic temperament.
Excellent lithium responders have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. The preservation of cognitive functions in long-term lithium-treated patients may be connected with the stimulation of the BDNF system, with the resulting prevention of affective episodes exerting deleterious cognitive effects, and possibly also with lithium’s antiviral effects.
A number of candidate genes that are related to neurotransmitters, intracellular signaling, neuroprotection, circadian rhythms, and other pathogenic mechanisms of bipolar disorder were found to be associated with the lithium prophylactic response. The Consortium on Lithium Genetics (ConLiGen) has recently performed the first genome-wide association study on the lithium response in bipolar disorder.