Breakthrough major depressive

Bipolar patients with so-called breakthrough major depressive episodes, despite adequate treatment, were placed in a randomized doubleblind 10-week study and treated with bupropion, sertraline, or venlafaxine augmentation (Post et al., 2001). Switches to hypomania or mania occurred in 14% of the patients. Those who responded positively to the treatment were continued for 1 year in a blinded maintenance trial, and 33% switched into hypomania or mania. In a second phase of their antidepressant augmentation studies, 18.2% switched into hypomania or... 

A breakthrough in the treatment of major depression was the discovery of fluoxetine, marketed as Prozac. Fluoxetine has a mechanism of action similar to that of imipramine with an important exception. It is a selective serotonin reuptake inhibitor, an SSRI. This strongly suggests that, in some sense, the symptoms of major depression result from a deficit in serotonin specifically. By inhibiting its reuptake from the synapse, the activity of serotonin is enhanced. Two other important drugs for major depression, sertraline (Zoloft) and paroxetine (Paxil), among several others,... 

Again there are relatively few studies that have investigated the use of carbamazepine in maintenance therapy. The results of the studies published suggest that carbamazepine is not as effective as lithium or divalproex. In the controlled studies of carbamazepine, the majority of patients required adjunctive treatment to prevent a breakthrough for the manic or depressive symptoms. 

The above project represents a novel approach and a possible new treatment for psychiatric disorder. The possibility that neuronal discharge short of total brain convulsion may have psychiatric effects would be a major advance in understanding the action of ECT. Moreover, a possible substitute treatment for ECT would be a major clinical breakthrough. TMS might allow us to stimulate deep brain regions without convulsions, pain, or known hazards. Before one widens the use of TMS in humans, further evaluation of the effectiveness of TMS in animal models for depression is necessary. Our hypothesis is that ECT exerts its therapeutic effects by stimulation of specific brain regions. We suggest that TMS may exert therapeutic effects without need for total brain convulsion. 

Historically the first sedative hypnotics to be introduced were the bromides in the mid 19th century, shortly followed by chloral hydrate, paraldehyde and urethane. It was not until the early years of this century that the first barbiturate, sodium barbitone, was developed and this was shortly followed by over 50 analogues, all with essentially similar pharmacological properties. The major breakthrough in the development of selective, relatively non-toxic sedative hypnotics followed the introduction of chlordiazepoxide in 1961. Most of the benzodiazepines in current use have been selected for their high anxiolytic potency relative to their central depressant effects. Because of their considerable safety, the benzodiazepines have now largely replaced the barbiturates and the alcohols, such as chloral hydrate and trichloroethanol, as the drugs of choice in the treatment of insomnia. 

Modem psychiatric treatments were introduced in 1948, when lithium carbonate was discovered as a treatment for mania by Australian psychiatrist John F. Cade. After Cade s initial report, lithium treatment was principally developed in Denmark by Mogens Schou (1918-), beginning in 1954. After a decade of trials by these and other groups in the USA and abroad, the Psychiatric Association and the Lithium Task Force recommended lithium to the Food and Drug Administration for therapy of mania in 1969, 20 years after its discovery by Cade. In 1970, the FDA approved the prescription drug. A breakthrough had finally been achieved in the treatment and prevention of one of the world s major mental health problems in the form of manic depression, and the genetically related forms of recurrent depression. 

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