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Which mood stabilizers are the most effective in reducing suicide rates in patients with bipolar disorder? This paper reviews the literature and compares the data on two types of mood-stabilizing agents, lithium and anticonvulsants. Compared with the large amount of data on lithium, there is surprising little information available on the effects of anticonvulsants on mortality in manic-depressive illness. Each was also assessed in terms of suicide risk factors such as depression and mixed episodes, rapid cycling, substance abuse, anxiety and panic, and central serotonergic function. Only two studies that provide data demonstrating anticonvulsant efficacy in preventing suicide in bipolar disorder are available, and the data are incomplete at best. Further research in this area should include an emphasis on the outcome of mortality in patients treated with any of the anticonvulsants or with lithium-anticonvulsant combinations.
The power of the life force is striking—in even among the most abominable conditions, like concentration camps, suicide remains relatively uncommon. Yet some human beings appear to harbor a powerful destructive force, which can under certain conditions manifest itself in violence, homicide, or suicide. Suicide has been with us since the beginning of history; it has often been romanticized, or viewed as an understandable escape from an intolerable situation. Philosophers and writers from William James to Albert Camus to Goethe have tended to view suicide as a window into the human condition, perhaps extreme but nevertheless a reflection of our shared humanity. However, highly reliable research has shown that suicide is, by and large, not a window into the human condition, but rather a manifestation of a disturbance—an abnormality of the human condition—a mental disorder.
Physicians know that the primary goal of medical treatment (after first doing no harm) is to prevent death. Death is the ultimate enemy in medical illness. In psychiatric illness, this enemy usually appears in the guise of suicide; the illness uses the hands of patients to wreak its havoc. To reduce mortality in psychiatric conditions, then, means to reduce suicide. It is indeed striking how little this matter has been analyzed. Little data are available on mortality with medications that are researched and approved for psychiatric illness. This would not be acceptable for medical illnesses outside of psychiatry today; it should not be the case in psychiatric illnesses either.
Bipolar disorders have a long history. Mania and melancholia are the oldest terms and descriptions within psychiatry, having been created in Homeric times by the Greeks, and conceptualized by Hippocrates and his school 2500 years ago. Aretaeus of Cappadocia put melancholia and mania together, because he recognized both psychopathological states as parts of the same disease, thereby giving birth to the bipolar disorders. His formulation stressed that, while mania has various phenomenological manifestations, nevertheless all of these forms belong to the same disease. Some of these special forms of bipolar disorder that are of major clinical and research relevance are the topic of this book.
Even though the three groups of bipolar disorders – mixed states, rapid-cycling, and atypical bipolar disorder – were well known by the nineteenth century, interest accelerated after the psychopharmacological revolution in the middle of the twentieth century. Thus the importance of defining rapid cycling was made clear by the observation that the response to lithium treatment was poorer in patients experiencing four or more episodes per year. The “rediscovery” of mixed states, which were conceptualized by Emil Kraepelin and Wilhelm Weygandt at the end of the nineteenth century, was also associated with problems concerning treatment with antidepressants and mood stabilizers. It has been half a century since the start of the pharmacological revolution. Its consequences across all fields of psychiatry have been enormous: biological research and genetics, treatment and prophylaxis, clinical and prognostic research, and psychopathological and diagnostic approaches.
The early descriptions and roots of mixed states are very closely connected with the history and development of concepts regarding bipolar disorders. These concepts have their roots in the work and theories of the Greek physicians of the classical period, especially of the school of Hippocrates and, later, of the school of Aretaeus of Cappadocia. Most of the studies of the families of patients with rapid-cycling bipolar disorder show no difference between rapid- and non-rapid-cycling patients. Schizoaffective disorders present as unipolar or bipolar forms in a way similar to mood disorders, as is reflected in both diagnostic and statistical manual of mental disorders (DSM-IV) and tenth revision of the international classification of diseases (ICD-10). ICD-10 and DSM-IV handle the definition of schizoaffective disorder differently. These differences present a difficulty for cross-national research. For a long time, agitated depression has been considered to be a type of mixed state.
Bipolar disorder manifests itself in a variety of forms. It can coexist with other psychiatric conditions, and treatment efficacy can depend on the type of bipolar state. This book covers the full range of atypical, rapid cycling and transient forms of bipolar disorder, from atypical and agitated depression to schizoaffective mixed states. The most recent ICD category is covered, and the authors also look at the biology and genetics of bipolar disorder, along with issues relating to age (children and the elderly), comorbidity, choice of drug treatment and investigational strategies.
Interest in the long-neglected neuropathology of major affective disorders has recently been rekindled, partly because of the emergence of brain-imaging techniques. We review the literature suggesting that attention be given to the neuroanatomy and neuropathology of primary and secondary affective disorders. Computerised tomography studies show that patients with affective disorders tend to be similar to schizophrenic patients and significantly different from normal control subjects in ventricle:brain ratio, sulcal widening, and cerebellar vermian atrophy. As yet, there are few neuropathological investigations of the brains of patients with primary affective disorders. Suggestions for further research in the neuropathology of affective disorders are offered.
The possible effects of clinical depression on intellectual function were investigated in unipolar and bipolar patients. Ninety-six hospitalized depressed patients completed the Wechsler Adult Intelligence Scale (WAIS) on admission and 34 were retested on remission. The high average full scale IQs found remained relatively stable throughout, consistent with earlier studies indicating a limited relationship between intellectual function and clinical severity of depression. No evidence was found for retarded psychomotor activity in bipolar groups or increased psychomotor activity in unipolar groups on three WAIS subtests of psychomotor function, but full scale IQ increased slightly in hypomania.
Cyclic 3′5′-adenosine monophosphate (c-AMP) was measured in cerebrospinal fluid (CSF) of manic and depressive patients with and without probenecid administration both before and during treatment with various psychotropic drugs. Oral probenecid (100 mg/kg) produced substantial c-AMP accumulations in CSF suggesting a probenecid-sensitive transport mechanism for c-AMP. Baseline and probenecid-induced accumulations of c-AMP were not significantly different in manic and depressed patients, while baseline levels in depressed patients were higher than those in neurological controls. Imipramine, amitriptyline, lithium, tryptophan, and electroconvulsant therapies did not significantly alter levels or accumulations of c-AMP in CSF of depressed patients.
Comprising seven essays by learned contributors and controversially advocating a rationalist Christianity, this work became a sensation upon publication in 1860. Frederick Temple (1821–1902), later Archbishop of Canterbury, wrote on the cultural contributions of non-Christians; Roland Williams (1817–70), Professor of Hebrew at Lampeter, questioned Old Testament prophesies; Baden Powell (1796–1850), Oxford Professor of Geometry, challenged belief in miracles and embraced Darwinism; Henry Bristow Wilson (1803–88) questioned literal biblical history; the only lay contributor, Egyptologist Charles Wycliffe Goodwin (1817–78), embraced geology; Mark Pattison (1813–84), tutor at Lincoln College, wrote on the history of rationalist theology; and Benjamin Jowett (1817–93), Oxford Professor of Greek, advocated a historical reading of the Bible. Wilson and Williams were later found guilty of heresy by a Church court, though this was overturned on appeal. For readers interested in the theological controversies of the Victorian era, these essays remain invaluable.