151,152 In contrast, a critical review of the literature by Long and Kathol153 found no clear evidence that methyldopa was associated with the development of depressive symptoms, in contrast to reserpine. Similarly, a review of 80 patients found no significant association between methyldopa and depression.154 Overall,

the association between methyldopa and depression is similar to that with β-blockers: suggestion of a connection Inhibitors,research,lifescience,medical in early case reports and small trials, with larger reviews unsupportive of a definitive association. Methyldopa, among its other actions, is a dopa decarboxylase inhibitor, and was reported to work synergistically with levodopa in patients with Parkinson’s disease in several early reports in the 1970s.155-157 However, there have been no recent reports to our knowledge, and it is not used in 5-HT receptor drugs clinical practice for this indication, having been replaced by the dopa decarboxlyase inhibitor, carbidopa. Finally, methyldopa has been Inhibitors,research,lifescience,medical associated with the onset of psychotic symptoms and acute confusional states, although these effects

are Inhibitors,research,lifescience,medical rare.158,159 Bottom line: Methyldopa is clearly associated with fatigue and sedation. In contrast to early studies linking methyldopa with depression, later reviews and studies have found this association to be relatively weak. Other neuropsychiatrie symptoms are uncommon. Reserpine Reserpine, an older antihypertensive medication that is now rarely used, can have

a variety of neuropsychiatrie effects. This agent acts by inhibiting the uptake Inhibitors,research,lifescience,medical of monoamine neurotransmitters into storage granules, resulting in the metabolism of these neurotransmitters by monoamine oxidase. This depletion of catecholamine neurotransmitters results in its antihypertensive effects and likely contributes to its association with Inhibitors,research,lifescience,medical depression and fatigue.47 Reserpine has long been associated with the onset of depressive symptoms, with a bevy of reports in the 1950s that linked reserpine use with depression,160-163 and a later review by members of our group citing an incidence of up to 15 %.164 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, but may not meet formal criteria for major Nature Medicine depression47,162; those who meet the full criteria tend to receive higher doses and to have a history of depression. Furthermore, two relatively large studies, one examining the onset of depressive symptoms among patients taking diuretics, pblockers, and reserpine in over 4000 patients,165 and a large study of hypertension in the elderly that used low doses of reserpine,166 found very low rates of depression with reserpine use.