BIPOLAR Subject

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

In a 2-year randomized double-blind study of the comparative efficacy of a mood stabilizer alone (lithium or valproate plus placebo) or a mood stabilizer added to quetiapine in 628 bipolar subjects, combination treatment resulted in fewer mood episodes (20%) versus a mood stabilizer alone (52%), and mania and depression were prevented to an equal degree [18 ]. 

We have already noted evidence for genetic factors that underlie the preference for and response to caffeine. These factors create a biologically based set of individual difference dimensions that may be modified by experience with the drug. In addition, there is evidence for a number of broader individual difference dimensions that appear to be relevant. These bipolar continua differentiate between subjects who are habitually high in arousal or arousability and those who are habitually low. The factors in question are personality dimensions that theoretically reflect underlying biological continua of arousal or arousability.238 Included among these dimensions are extraversion,58 impulsivity,239240 and sensation-seek-ing.94-241-242 We will take up the first two of these. 

Chen, Y. W. and Dilsaver, S. C. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol. Psych. 39 896-899,1996. 

Souetre, E., Salvati, E., Wehr, T. A. et al. Twenty-four-hour profiles of body temperature and plasma TSH in bipolar patients during depression and during remission and in normal control subjects. Am. J. Psychiatry 145 1133-1137, 1988. 

The HPA axis has been hypothesised to be of aetiological importance in depressive illnesses (McAllister-Williams Young, 1998 McAllister-Williams et al., 1998). Severely depressed patients (Sachar et al., 1973) and bipolar disorder patients (Linkowski et al., 1985) have signihcantly raised cortisol concentrations compared to controls. Imaging studies show an enlargement of the adrenal cortex in depressed patients compared to healthy subjects (Nemeroff... 

Fatemi, S.H., Earle, J.A., and McMenomy, T. (2000) Reduction in reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry 5 654-653. 

Initial pharmacogenetic studies of serotonin transporter gene (HTT) variants used case-control methods and have generated disparate results in different populations. Positive association of the promoter VNTR polymorphism (5-HTTLPR) with clinical response to fluvoxamine was seen in Italian patients with bipolar or unipolar delusional depression subjects with one or... 

Friedman, L., Findling, R.L., Kenny, J.T., Swales, T.P., Stuve, T.A., Jesberger, J.A., Lewin, J.S., and Schulz, S.C. (1999). An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects. Biol Psychiatry, 46 78-88. 

The relative absence of systematic studies of bipolar patients under age 18 forces clinicians to extrapolate data from adult studies. There are four major types of studies that provide information on subjects with bipolar disorder double-blind, placebo-controlled studies of patients with acute mania prospective open-label studies of patients with bipolar disorder (which includes mania, hypomania, manic symptoms, or bipolar NOS, people at risk for mania because of their family history, and those with a history of mania who are not currently manic) case series and anecdotal reports. 

Of the atypical antipsychotics, clozapine, olanzapine, and risperidone have been studied the most. Clozapine was used to treat 10 treatment refractory acutely manic patients and 15 schizomanic patients. Using reduction in the YMRS score as the outcome measure, 72% improved (non-rapid cycling, bipolar patients). Comparison of olanzapine (5-20 mg) with placebo showed significant reduction of the YMRS in 49% vs. 24% of subjects by 3 weeks, with significant change evident by the first week. In a trial comparing risperidone at 6 mg with haloperidol at 10 mg and low-dose lithium (800-1200 mg/day) efficacy was similar over the 28 days of the trial. 

There are three reports (Hsu and Starzinsi, 1986 Woolston, 1999 Craven and Murphy, 2000) on a total of six bipolar adolescents treated with CBZ—three with acute mania, two of whom responded (Hsu and Starzinski, 1986). As in studies of adults, antipsychotic and/or antianxiety medications were frequently used adjunctively in subjects of these reports. Gabapentin, topiramate, and lamotrigine have been minimally studied for the treatment of acute mania in youth. Davanzo and McCracken review these limited data in Chapter 25 in this volume. 

Kupfer 1987 Soldatos et al. 1987). However, despite these intergroup differences, a subgroup of depressed patients may actually sleep more than the control subjects (Garvey et al. 1984 Kupfer 1984 Michaelis and Hofmann 1973) this subgroup includes mainly patients with seasonal affective disorder (Rosenthal et al. 1984) and those with anergic depression of the bipolar type (Detre et al. 1972 Kupfer et al. 1972). 

Because melatonin is sold over the counter and its production is not the subject of strict regulation as is that of prescribed medications, it is in wide use, but insufficient scientifically controlled information is available. Another consequence of the popularity and availability of the hormone is its use in a wide array of situations in which its efficacy has not been proven yet for instance, as treatment for neurodegenerative diseases or as a sleep-inducing medication. It also has been tried as an antidepressant, but that effect is still unclear. The administration of melatonin to patients with bipolar depression, especially to rapid cyclers, is of interest, especially if its use is associated with the presumed decrease in nocturnal hormonal levels and increase in sensitivity to light (Lewy et al. 1985). The possibility that melatonin also serves as a stabilizer of rhythm in these patients is in accord with the homeostatic effect of several other hormones that have been previously discussed here. 

Emamghoreishi M, Schhchter L, li PP, et al High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder. Am J Psychiatry 154 976-982, 1997... 

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