Ready To Rock
3 weeks ago
"The most dreadful thing that can happen to a man is to become ridiculous in his own eyes in a matter of essential importance, to discover, for example, that the sum and substance of his sentiment is rubbish." Søren Kierkegaard
Interest in the much-debated possibility of genetic overlap between schizophrenia and bipolar disorder has been restimulated by molecular genetic studies, which have led to reappraisal of previous evidence from genetic epidemiology. Most previous genetic epidemiological studies have been underpowered to investigate the question of diagnostic overlap. This study, however, included more than 2 million nuclear families; the researchers merged data from the Swedish multigeneration population register and the Swedish hospital discharge register. The results clearly show increased risks of both schizophrenia and bipolar disorder for first-degree relatives of probands with either disorder. Furthermore, evidence from half-siblings and offspring adopted away shows that this is due substantially to genetic factors.
No experienced psychiatrist will deny that there is an alarmingly large number of cases in which it seems impossible, in spite of the most careful observation to make a firm diagnosis... it is becoming increasingly clear that we cannot distinguish satisfactorily between these two illnesses and this raises the suspicion that our formulation of the problem may be incorrect. (1920)
As regards the generality of 'psychosis', it seems clear that there are definite genetic links between different diagnostic categories (schizophrenia, manic-depressive disorder, schizo-affective disorder, unipolar disorder) which make it impossible to regard them as entirely separate disease entities. Some specificity there undoubtedly is, but there is also a generality of disorder which links all these disorders and their sub-classifications and diagnoses together to form one end of the psychoticism continuum, with a severity gradient placing schizophrenia at the extreme end, followed by schizo-affective disorder, manic-depressive disorder and finally unipolar illness.
[The researchers] found that users of the newer drugs were 2.26 times more likely to suffer from sudden cardiac death than those not on the medications.
Patients who took the highest doses were at the highest risk. Overall, the patients had a three-in-1,000 risk of sudden cardiac death a year [...]
The drugs appear to cause problems by disrupting potassium in the heart, causing its electrical rhythm to fail [...]
Dr. Sebastian Schneeweiss, an associate professor of medicine and epidemiology at the Harvard School of Public Health, co-wrote an accompanying commentary in the journal. He said that, considering the risk and lack of evidence that the drugs are useful beyond limited cases, doctors should "sharply" reduce their use to treat conditions other than acute psychosis and schizophrenia.
Background Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy.
Methods A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n=372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia–Change Version subscale scores for depression and mania, and Global Assessment of Function scores.
Results The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores.
Conclusions The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.
Several factors may have contributed to the surprisingly good outcomes in the placebo group. Patients with mild forms of bipolar disorder may have been selected for the study because of the enrollment requirement that 2 consecutive GAS scores had to be above 60. Bias may also have been introduced by the requirement that remission of mania had to be achieved within 3 months of the manic episode, as failure to meet this criterion was a major reason for exclusion from randomization. Also, some patients were randomized whose manic episodes resolved without specific treatment. In addition, a number of study candidates with histories of severe illness were reluctant to enroll in the study because of the chance of receiving placebo for up to 1 year, with minimal use of rescue medications. Moreover, the index episodes of mania seemed to be more severe in patients who failed to qualify for randomization than in those randomized. Drug-placebo differences are known to be greater when patients with more severe forms of illness are studied.