Answer to Question 1
The actions and behavioral effects of reserpine (depletes monoamines, reduces manic symptoms, induces depression), MAOIs (allow cytoplasmic concentrations of monoamines to increase, reduce symptoms of depression), amphetamine (increases extraneuronal monoamine levels, enhances mood), and monoamine reuptake blockers (increase extraneuronal monoamine levels, reduce symptoms of depression) are superficially compatible with the hypothesis, but the fact that MAOIs and many antidepressants enhance monoamine levels within hours but exert their benefits in depressed individuals over several days or weeks is a problem for the hypothesis. Also, clinically effective antidepressants only elevate mood in depressed individuals. Also, treatments that acutely deplete the brain of NE or 5-HT in normal adults without a history of depression do not induce the core symptoms of depression.
Answer to Question 2
Primarily due to their ability to produce a hypertensive crisisa very serious toxic effect that can lead to headaches, fever, intracranial bleeding, and possible deathif the patient also takes adrenergic enhancing drugs or foods containing tyramine and other monoamines. They have a reputation of not being as effective as the tricyclic antidepressants or SSRIs, although empirical research indicates that their overall efficacy in reducing the symptoms of clinical depression is comparable.
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