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." In the 19th century gout and kidney stones were unsuccessfully treated with lithium." In the mid- to late 1940s, John F.J.Cade, MD started experimenting with lithium." In 1949 Dr Cade s research demonstrated that lithium successfully treated mania." In the late 1940s lithium was tragically used as a salt substitute for patients with heartdisease, high blood pressure, and other medical problems, resulting in numerouslithium poisonings and several deaths. Treating bipolar disorders 101" Lithium became extremely unpopular and questioned after the salt substitute tragedy,which may have played a role in delaying its use as a drug for treating bipolardisorders." Mid-1940s British and American psychiatric training programs and clinics embracedpsychoanalytical theory and questioned the value of using medications for treatingmental illness." During the mid-1940s the end of World War II left mental health research in Germanyand much of Eastern Europe in disarray." German experimentation on Jews and prisoners caused many to reject research that altered brain functioning and helped to reinforce psychoanalytical explanations formental disorders." 1950s Danish researchers led by Mogens Schou systematically researched theproperties, dose requirements, and safe management of lithium for treating bipolardisorders." In the 1960s lithium received general acceptance within the psychiatric community." In 1967 Mogens Schou and associates empirically demonstrated that lithium not onlytreats bipolar symptoms but for some patients prevents future depressive and manicepisodes." By the 1970s lithium became the first line of treatment for bipolar disorders throughoutthe United States." From the late 1960s to the present, lithium was found to be effective for treating bipolardepression and caused fewer patients to switch into a manic episode compared withantidepressants." In the early 2000s lamotrigine was found to be more effective for treating bipolardepression than lithium." In the early 2000s lithium was found to be more effective for treating manic episodesthan lamotrigine.nent research studies, the APA Guidelines expressed substantial clinical confidence inlithium for treating bipolar depression and moderate confidence in the use of lamotrigine.As research documents lamotrigine s effectiveness and safety, future panels may give thedrug a stronger recommendation.Lamotrigine, developed by GlaxoSmithKline and marketed under the brand nameLamictal®, is the first medication since lithium to be approved by the United States Foodand Drug Administration (FDA) for long-term maintenance treatment of patients withbipolar I disorder.The medication has shown effectiveness in delaying or preventingmania, hypomania, mixed episodes, and depression.Data from randomized studiesindicates that lamotrigine is particularly robust in protecting patients from bipolardepression34 36.Moreover, an 18-month multicenter placebo-controlled study found thatboth lamotrigine and lithium delayed the onset of mood episodes, but lamotrigine wasmore effective in preventing depressive episodes37.Additionally, lamotrigine used as amonotherapy for depressive and manic episodes did not increase symptoms or acceleratemood cycling.The researchers found that approximately 4.6 5.4% of research patientstreated for bipolar depression with only lamotrigine switched into either a hypomanic or amanic episode, compared with 5% of patients on placebo35,37,38. Atlas of bipolar disorders 102Figure 6.4 Results of lithium treatmentfor manic symptomsAdditionally, there is evidence from a small study that lamotrigine is an effectivemonotherapy for bipolar II depressive and manic symptoms.The study compared patientfunctioning and symptoms for 6 months on lamotrigine and an SSRI, and for 6 months onjust lamotrigine therapy.While on lamotrigine monotherapy, the patient group hadsignificantly fewer depressive and manic episodes, episodes were shorter in duration, andpsychosocial functioning as measured by the Global Assessment of Functioning (GAP)scale increased39.Even though these results are extremely promising, a definitivestatement about lamotrigine s effectiveness as a monotherapy for bipolar II disorderscannot be given until further research is completed.In addition to this drug s apparent effectiveness in treating bipolar I and II depression,there is also evidence that, compared with placebo, long-term use of lamotrigine does notcause patients to experience significant body weight gain.There is also preliminaryevidence that lamotrigine causes fewer tremors and cognitive problems compared withlithium40 42.Lithium can cause subtle neurocognitive impairment in psychomotor speed,immediate and delayed verbal memory, and other executive functions43.It is less clearwhether lithium used for maintenance interferes with attention and concentration.Thereis no evidence, however, that lithium taken as a long-term maintenance therapy causesongoing cumulative neurocognitive damage44.While lamotrigine does not appear todecrease neurocognitive functioning, in rare cases it can cause a serious skin rash.Amulticenter study reported that more patients on lamotrigine developed rashes than didindividuals onLamotrigine Overview" Lamotrigine is an anticonvulsant medication." It is FDA-approved (2003) as a long-term maintenance drug for treating chronic bipolarsymptoms. Treating bipolar disorders 103" It has been found to be effective for controlling and decreasing bipolar depression." The rate of medication-triggered mood switching is low and similar to placebo." Lamotrigine is more effective than lithium for controlling bipolar depression." It is effective for treating mania, but less so than lithium.a placebo.However, the number of rashes in each group was similar and statisticallyinsignificant45.The promise of decreased medication side-effects can tempt consumers to push for animmediate change in their drug therapy
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