Antidepressants mental effects

Iproniazid and imipramine seemed to work as antidepressants, but how did they achieve their effects It would be another decade before the chemical-imbalance theory was launched. In 1965, Joseph Schildkraut at the National Institute of Mental Health in Washington, DC, published a groundbreaking paper in which he argued that depression was caused by a deficiency of the neurotransmitter norepinephrine in the gaps between neurons in the brain.8 Two years later Alec Coppen, a physician at West Park Hospital in Surrey, published another version of the chemical-imbalance theory. His version differed from Schildkraut s in that it put most of the blame on a different neurotransmitter, emphasizing serotonin rather than norepinephrine as the neurotransmitter that was lacking.9... 

Hypomania and use with other antidepressants One case has been reported of concurrent use of hypericum with an SSRI. Gordon (1998) reported a case of a 50-year-old woman taking 600 mg/day of hypericum for chronic depression. She had discontinued taking Paxil 10 days prior to hypericum and experienced no ill effects at that time. However, she added 20 mg of paroxetine to her regimen of hypericum to improve her sleep. She presented with lethargy, nausea, and weakness, but vital signs and mental status were normal. Following discontinuation of medications, she returned to normal status the next day. 

Shortly after iproniazid was shown to have antidepressant properties, imipramine was introduced as the first tricyclic antidepressant. These drugs received the name tricyclic because their structure contains three molecular rings. At first, imipramine was investigated as a possible treatment for the psychotic episodes associated with schizophrenia, a severe mental disorder that causes hallucinations and delusions, because it was chemically similar to another effective anti-schizophrenia drug. Imipramine did not reduce the severity of psychotic episodes, but it did elevate the mood of the patients who took it. In the late 1950s, it was released in the United States under the name Tofranil for the treatment of depression. 

Because the various transmitter systems in the brain are directly and indirectly linked together, purely catecholaminergic or purely serotoninergic depressions are unlikely. Furthermore, the majority of antidepressants known today have multiple effects, especially after repeated administration, and thus affect a number of transmitter systems. This fact is taken into account by more recent hypotheses of depression in that a balance between several transmitter systems is postulated as a prerequisite for mental health, whereas affective psychoses are believed to be a reflection of an imbalance. 

The study by Elkin et al. (391) from the National Institute of Mental Health Treatment of Depression Collaborative Research Program suggested that antidepressants had superior efficacy in the treatment of moderate to more severe episodes of major depression (i.e., 17-item HDRS score of 20 or more). In response to that claim, DeRubeis et al. (396) performed a metaanalysis of four studies and found that CBT was as effective as several different antidepressants in such cases. More recently, Keller et al. (397) found that a variant of CBT called cognitive-behavioral analyses (CBAS) therapy was as effective as nefazodone (mean dose = 460 mg per day) in producing both response and remission in outpatients with moderate to more severe chronic depression. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

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