The number of American children and adolescents treated for bipolar disorder increased 40-fold (4,000 times) from 1994 to 2003, researchers say the number continues to rise even faster.  http://www.nytimes.com/2007/09/04/health/04psych.html

Is Bipolar Life Long? Do Drugs Improve Outcome? 

NO, Not according to the research...

(Major Research Contribution from author Robert Whitaker.  A must purchase is http://www.madinamerica.com/Mad%20In%20America/Author.html  and watch for his new book on Bipolar Disorder, coming out soon...

Michael Tsuang and his collegues did a 35 year followup study of people admitted with first time mania to a hospital, and found 64% with complete recovery.  (Archives of Gen. Psychiatry, 36, 1295-1301).  I have seen this in my own practice as well.

Zarate, Functional Impairment and cognition in bipolar disorder. Psychiatric Quarterly, 71, no. 4, winter 2000. 309-329.  This is a review article in which they note that long-term outcomes for bipolar are much worse than in the pre-drug era, and they speculate that use of antidepressants and neuroleptics may be causing the worsening of long-term outomes.

Winokur, a professor at Washington University, states in his book Manic Depressive Illness. 1969  “The outcome of manic depressive disease is characterized by not becoming chronic . . . patients may have one or more attacks, with symptom-free intervals. When the patients recover, there is no difficulty resuming their usual occupations.” 

In Lundquist’s 1945 study, he identifies 95 manic patients. 75% well by 10 months; 42%  became ill once more in course of 20 years, I believe. 85% socially recovered. Only 8.5% developed a chronic course. 

Pollack studies 8,000 manic depressive cases from 1909 to 1920, from NYS Department of mental hygiene. In this period of time, over half had not had a second attack. Only 20% suffered 3 attacks or more.

 In an article on suicide prevention, Kay Redfield Jamison and Keith Hawton (2005-'The burden of suicide and clinical suggestions for prevention" in K. Hawton (Ed.) "Prevention and Treatment of Suicidal Behavior: From Science to Practice," 183-196, Oxford: Oxford University Press), noted psychotherapy plays a vital role in suicide prevention in bipolar patients (e.g. hospitalization rates lower an social functioning better).  Redfield, K., Hawton, K., 2005, Psychotherapy of bipolar disorder: a review, In Suicide Prevention, Volume 80, Issues 2-3, June 2004, Pages 101-114.  From University of Manchester, Manchester, UK, Received 14 November 2002;  accepted 8 April 2003.
 

Goodwin  cites five studies from the pre-drug era that followed patients from 10 to 32 years. He shows chronic rates ranging from one to 11 percent; the fifth, a very small study said 56%. A sixth 35-year followup study of 100 patients that was published in 1979, and thus spills over a bit into the drug era, said 22% became chronic, 14% had fair outcomes, and 64% had good outcomes.

Drugs Make it Worse

In 2000, Zarate Paper.  Zarate, Functional Impairment and cognition in bipolar disorder. Psychiatric Quarterly, 71, no. 4, winter 2000. 309-329.

 This group of researchers, which is from the Bipolar and Psychotic Disorders Program at the University of Massachusetts, reviewed the decline in outcomes.  The problem: “In the era prior to modern pharmacotherapy, poor outcome in mania was considered a relatively rare occurrence . . . In contrast, more modern do not describe such a favorable outcome in patients with bipolar disorder. “

 The cause: “Medication induced changes may be yet another factor in explaining the discrepancies in recovery rates between earlier and more recent studies. It is possible that as clinicians e have been contributing to a worsening of the course of the illness.”

 Problems: a) Antidepressants increase risk of switching and rapid cycling, b) Antipsychotics increase depressive episodes, c) Neuroleptics lead to lower functional recovery rates as well

 2003. Ghaemi, “Antidepressants in bipolar disorder: the case for caution.” Bipolar disorders 2003:5 421-33.  In his review, he concludes: "There are significant risks of mania and long-term worsening of bipolar illness with antidepressants.”  The antidepressants lead to “an increased risk of cycle acceleration with antidepressants.” A three-time increase in manic episodes. Associated with rapid cycling in at least 20% of patients.  The use of antidepressants leads to “long-term mood destabilization” in a significant percentage of patients.

2008. Ghaemi. Treatment of Rapid-cylcing Bipolar disorder: Are Antidepressants mood destabilizers? AJP, 165:3, March 2008.  Rapid cycling is first identified in the 1970s, after introduction of lithium. These patients do worse in long-term followup.  New data from Schenck (above) note that “the major predictor of worse outcome was antidepressant use, which about 60% of patients received.”   “This shows that “antidepressants are associated with worsened course of illness even after adjustment for severity of baseline depression.”  In my own clinical experience, “most cases of refractory bipolar disorder, usually of he rapid cycling variety, are due to the mood-destabilizing effects of antidepressants.” He notes this is different from an AD-induced switch to mania. “Mood destabilization is a long-term phenomenon, reflecting more mood episodes over time than would have occurred by natural history.”

Lithium:

A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder.  This is the first controlled study of maintenance treatment of bipolar disorder in more than 25 years.  372 subjects were followed for one year.  Placebo relapse was only 38%, and it did as well as either drug, with far fewer adverse effects.  The discussion that followed (by Baldessarini, Tohen and Tondo) was about why the placebo group had such "surprisingly good outcomes," and what can be done in future studies to make sure the drugs compare better. Bowden C, Calabrese J, McElroy S, Gyulai L, Wassef A, Petty F, Pope H, Chou J, Keck P, Rhodes L, Swann A, Hirschfeld R, & Wozniak P, for the Divalproex Maintenance Study Group. Arch Gen Psych. 2000;57:481-489  http://archpsyc.ama-assn.org/issues/current/full/yoa8223.html

Efficacy of lithium in mania and maintenance therapy of bipolar disorder, By Bowden C. J Clin Psychiatry 2000:61[suppl 9]:35-40.   Bowden finds it "surprising" that "little attention has been given to component behaviors most specifically affected by lithium." He compiled data from three of his own controlled studies and an unpublished study by Swann to show that lithium slows motor activity much more than placebo, but is equal to placebo in its effects on elevated mood and sleeplessness. Lithium's effect may extend to "reduction of normal as well as elevated activity levels." In an unpublished study by Bowden, Katz, and Swann (2000), lithium slowed activity to a level below that of normal controls.

1994. Baker, J.P. Outcomes of Lithium Discontinuation, Lithium, 5, 187-192.   There was evidence that many people with manic-depressive illness would suffer a second episode at some time, and thus it would be good to have a drug that could prevent this. Lithium became the drug of choice for a time. The studies that proved this had this design: You took patients who were stabilized on the drug and then divided into two groups: One would be withdrawn, usually abruptly, and the other maintained on the drugs. Metanalysis of 19 such studies. Results:  53.5% of those withdrawn from lithium relapsed and 37.5% of those on lithium relapsed.  Gradual withdrawal. However, within those 19 studies, the researcher found several where he could group patients according to whether they had undergone slow withdrawal (greater than a two-week period.) Small patient sample, but only 23 of 78 patients relapsed, or 29%.   The importance of this is that the slow withdrawal method had a lower relapse rate than those maintained on lithium. So is lithium preventing relapse, or are what you seeing is that once you go on lithium, you are at high risk of relapse if you come off it quickly?

Chandran, H., Chakraborty, N. and Healy, D., The impact of mood stabilizers on bipolar disorder: the 1890s and 1990s compared, In Hist Psychiatry. 2005 Dec;16:423-34,  The below study compared patterns of service utilization by bipolar patients in North-West Wales and found a greater prevalence of service utilization in the 1990s compared with the 1890s. In the pre-lithium era, admissions for bipolar disorders occurred at a rate of 4 every 10 years; they now occur at a rate of 6.3 every 10 years. Where 100 years ago, there were 16 bipolar patients per million population resident per day in hospital, there are now 24 per million resident in acute service beds and more in non-acute beds. These data are incompatible with simple claims that mood stabilizing drugs 'work'.

Lithium: Adverse Effects and Interactions.  Gitlin MJ, Jamison KR. 1984. Lithium Clinics: Theory and Practice. Hosp Comm Psychiatry. 35:363-368.  The high frequency of non-adherence to lithium treatment (30-50%) is often associated with adverse effects, particularly in the early stages of treatment. Cognitive impairment, tremor, acne, polyuria and polydipsia, muscle weakness and weight gain can be associated with noncompliance, particularly in adolescents, young adults and the elderly. (Gitlin et al, 1984). Long term adverse effects on thyroid functioning and the kidneys, especially in patients with a previous or family history of renal problems, suggest the value of caution and the usefulness of regular monitoring. Lithium has teratogenic potential, albeit posing less risk than previously stated for Ebstein's cardiac anomaly, and lower risk when compared with the anticonvulsants. Lithium has a narrow therapeutic range and toxicity can be induced by changes in electrolyte and fluid balance. Lithium can be lethal in overdose.   Many medications interact adversely with Lithium. Commonly, this results from alterations in serum concentrations of either Lithium or the concomitant medications. Potential for neurotoxicity with Carbamazepine, decreased serum lithium levels with calcium channel blockers and xanthines, and increased serum levels with most psychotropics, thiazides and ACE inhibitors should be borne in mind. Patients should be informed about these potential interactions in advance, and screened closely for the use of other medications, including over the counter medications, when side effects appear.