Treatment

Lithium is the gold standard in the treatment of bipolar disorder.  It is clearly the best tested treatment for bipolar disorder and the rates of suicide deaths are far lower on lithium than valproate and also lower than with carbamazepine.  

Apart from lithium, other treatments help primarily either mania or depression.  Depression is the most disabling for the large majority of patients suffering from bipolar or manic-depressive illness.  Most of my material for treating depression is covered under depression.

There is a big push at present by the pharmaceutical companies manufacturing lamotrigine (Lamictal), a seizure medication, and the various atypical anti-psychotics.  While atypical anti-psychotics have been shown to be of value for patients having a manic episode, their long-term effectiveness at preventing suicides for either patients coming out of a manic or a depressive episode is unknown.  Lamotrigine actually works better for depression than mania, but is far from a miracle treatment.  In fact, it has not been compared to any of the much less expensive antidepressants currently available.  Atypical anti-psychotics are also quite expensive, but frequently useful.

For individuals with side-effects to lithium or where lithium alone is not enough to control manic episodes, in addition to atypical anti-psychotics, there are carbamazepine (Tegretol), and valproate (Depakene and Depakote).  These can be taken together with lithium or without lithium depending on the patient.  Depakote is markedly inferior to lithium in preventing suicides and might even increase suicides.  Oxcarbazepine (Trileptal) is useful where carbamazepine would interact adversely with other medications that a patient might have to take, but should be reserved for those instances due to its high cost.

Many anti-depressants, especially bupropion because of its somewhat lower risk of triggering a manic episode, are also of value for depressive episodes where lithium is not enough.  Antidepressants are usually not used without one of the above anti-manic agents to block high swings.  Occasionally, carbamazepine, valproate, or an anti-psychotic will prevent depressive episodes, but they are not usually very effective at this.  Even lamotrigine is probably inferior to many antidepressants.  Other useful interventions in addition to the above medication may include fish oil, folic acid, exercise, counseling, and in selected cases thyroxine.  A single small double-blind study suggests that phenytoin (Dilantin) lowers the risk of relapse.

Gabapentin (Neurontin) is not listed as an alternative, since three double-blind studies have so far documented it to be of no value for bipolar disorder.  The gabapentin research can be found under Dubious Research.  Topiramate (Topamax) has no scientific evidence of being of any use for bipolar disorders, with just one failed double-blind trial to date.  Gabapentin and topiramate are two seizures medications which were irresponsibly promoted by their drug companies and psychiatrists receiving money from those companies.  The gabapentin manufacturer was fined $200,000,000 by the U.S. government for its illegal promotion of gabapentin for bipolar disorder.  There are still psychiatrists who earn money working for various drug companies who keep writing articles claiming that some of the other new seizure medications might be worthwhile for bipolar disorder, there is absolutely no scientific evidence to support such speculation.

Earlier Onset Bipolars with Bipolar Parent or if Born after 1940: first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. Univ Pittsburgh. Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry. Chengappa KN, Kupfer DJ, Frank E, Houck PR, Grochocinski VJ, Cluss PA, Stapf DA. Am J Psychiatry. 2003 Sep;160(9):1636-42

Bipolars Much More Often Depressed: 146 bipolar I patients followed for 12.8 years were assessed weekly. Depressive symptoms were present for 32% of the weeks, manic/hypomanic (9%) or cycling/mixed states (6%). 14% had minor depression/dysthymia, 9% subsyndromal depression, and 9% a major depression. In addition, the study indicated that depression as the index episode predicted a greater chronicity. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530-537; 86 bipolar II patients over 13.4 years had depressive symptoms 50% of the weeks vs. 1% for manic/hypomanic and 12% for cycling/mixed states. Minor depression was seen in 24% of the weeks, 14% subsyndromal depression, and 13% major depression. Depressive episode lasted longer with a lower rate of recovery. Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60:261-269.

Australian National Study of Bipolars: Induction of mania reported by Tohen: venlafaxine had a rate of 13%, lamotrigine of 5.3%, olanzapine/fluoxetine of 6.4% and, in 1 study of SSRIs, of 3.7%.

Rehospitalization Rates: One-year rehospitalization rates of patients with bipolar disorder discharged on a mood stabilizer alone, a mood stabilizer plus a typical antipsychotic, or a mood stabilizer plus an atypical antipsychotic were 23% for a mood stabilizer alone, 27% for a mood stabilizer plus a typical antipsychotic, and 25% for a mood stabilizer plus an atypical antipsychotic ( esp. olanzapine and risperidone) were rehospitalized within 1 year of discharge. The number of previous psychiatric hospitalizations contributed to the risk of readmission. Risk factors and medication costs should be considered when designing the optimal treatment plan for an individual patient. Long-term prospective studies are needed. Rehospitalization Rates of Patients With Bipolar Disorder Discharged on a Mood Stabilizer Versus a Mood Stabilizer Plus an Atypical or Typical Antipsychotic. Patel NC, et al. University of Texas at Austin. J Behav Health Serv Res. 2005 October/November/December;32(4):438-445.

Religion Important to Many Patients and May Conflict: A questionnaire survey of bipolar patients found most patients held strong religious or spiritual beliefs (78%) and practiced their religion frequently (81.5%). Most saw a direct link between their beliefs and the management of their illness. Many used religious coping, and often religious-spiritual beliefs and practice put them in conflict with illness models (24%) and advice (19%) used by their medical advisors. Univ Otago, New Zealand. Spiritual beliefs in bipolar affective disorder: their relevance for illness management. Mitchell L, Romans S. J Affect Disord. 2003 Aug;75(3):247-57

Medication Compliance Markedly Reduced Rearrest: In a very small study of probation records of all adolescents (N = 31) released during a 1-year period from a county juvenile corrections treatment facility who had DSM-III-R bipolar disorder, were stabilized on medication, and had agreed to continue treatment at an adolescent psychiatry clinic, the number of serious offenses (felonies and misdemeanors) was significantly reduced while subjects were on medication (4 offenses in 2992 days) versus off medication (39 offenses in 6108 days) (p < .0001). The off-medication rate of offending was 4.8 times higher than the on-medication rate. Probation violations were also significantly reduced while subjects were on medication (p < .001). Recidivism in medication-noncompliant serious juvenile offenders with bipolar disorder. Dailey LF, Townsend SW, et al. Hennepin County Medical Center, Minneapolis. J Clin Psychiatry. 2005 Apr;66(4):477-84.

Placebo Studies Safe for Mania: In a review of all placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic/depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands between 1997 and 2003, the 11 studies of acute manic episode, including 1,506 patients (117 person-years) in the treatment group and 1,005 patients (71 person-years) in the placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic/depressive episode, including 943 patients (406 person-years) in the treatment group and 418 patients (136 person-years) in the placebo group, two suicides (493/100,000 person-years of exposure) and eight suicide attempts (1,969/100,000 person-years of exposure) occurred in the treatment group, but no suicides and two suicide attempts (1,467/100,000 person-years of exposure) occurred in the placebo group. Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode. Storosum JG, Wohlfarth T, et al. Medicines Evaluation Board of the Netherlands. Am J Psychiatry. 2005 Apr;162(4):799-802.

Lithium, Carbamazepine, Valproic Acid All Decrease Arachidonic Acid But Not DHA Incorporation Into Brain; Topiramate Doesn't: Similar to lithium and valproic acid, chronic carbamazepine, compared with vehicle, decreased the rate of incorporation of arachidonic acid-CoA (27%-29%) and turnover of arachidonic acid (25%-27%) but not of DHA-CoA or DHA in brain phospholipids. Chronic Carbamazepine Decreases the Incorporation Rate and Turnover of Arachidonic Acid but Not Docosahexaenoic Acid in Brain Phospholipids of the Unanesthetized Rat: Relevance to Bipolar Disorder. Bazinet RP, et al. National Institute on Aging, National Institutes of Health, Bethesda, Maryland. Biol Psychiatry. 2005 Sep 20. However, topiramate, which does not help Bipolar Disorder, does not have this effect on arachidonic acid. Lee, HJ, et al NIMH. Neurochem Res. 2005 May;30(5):677-83.

Thomas E. Radecki, M.D., J.D.

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