53 Rarely, mood disturbance has been described with clonidine; pooled information suggests that depression occurs in approximately 1% to 2% of patients. There are no case E7080 reports of clonidine-induced depression or mania, though there has been one report of hypomania upon withdrawal of clonidine.66 Methyldopa, another centrally acting antihypertensive Inhibitors,research,lifescience,medical medication, is infrequently used in clinical practice (except in those with pregnancy-induced hypertension).

It may reduce blood pressure via central α-2 agonism, and may also act as a false (norepinephrine) neurotransmitter.53 As with many cardiovascular agents, common side effects are sedation and fatigue; sedation occurs in approximately one third of methyldopa-treated Inhibitors,research,lifescience,medical patients, with high rates of associated fatigue.67 However, perhaps the best-known neuropsychiatric consequence of methyldopa use is depression. Depressive symptoms may occur more frequently with methyldopa than with most other antihypertensive agents, and it is thought that this effect may be related to reduced norepinephrine levels. An early study of methyldopa found increased Inhibitors,research,lifescience,medical rates of depression, especially in those with a history of depression,68

and a study of elderly patients found methyldopa to be more strongly associated with depressive symptoms than were ß-blockers69; overall, it appears that Inhibitors,research,lifescience,medical reported depressive reactions to methyldopa often occur in those with prior depressive episodes.70 In contrast, a review of the literature by Long and Kathol71 found no clear evidence that methyldopa (in contrast to reserpine) was associated with depressive symptoms. Similarly, a review of 80 patients found no significant association Inhibitors,research,lifescience,medical between methyldopa and depression.72 Reserpine Reserpine, an older antihypertensive medication that is now rarely used, can have a variety of neuropsychiatric effects.

This agent acts by inhibiting the sequestration of monoamine neurotransmitters into storage granules, resulting in the metabolism of these neurotransmitters by monoamine oxidase (MAO). This depletion of catecholamine neurotransmitters results in its antihypertensive effects and likely contributes to its new association with depression.53 Reserpine has long been associated with depressive symptoms with a number of reports in the 1950s that linked reserpine use with depression,73 and a later review citing an incidence of up to 15 %.74 However, other (generally more recent) reports call this association into question. First, the depressive symptoms associated with use of reserpine appear to include sedation, malaise, and fatigue.53,75 Patients with these symptoms alone may not meet formal criteria for major depression but instead exhibit subsyndromal depression.53,75 Those who do meet full criteria tend to receive higher doses and to have a history of depression.