The effects of acute scopolamine in geriatric depression. Scopolamine alone or combined with ephedrine in seasickness: a double-blind, placebo-controlled study. Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations. Sleep electroencephalographic abnormalities in adolescent depressives: Effects of scopolamine Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder.
In an intensive multidrug , multidose study , nine elderly depressed patients were administered 0.1 , 0.25 , and 0.5 mg of scopolamine hydrobromide , 1 mg of oral lorazepam , and placebo in a double-blind investigation aim ed at assessing the status of the central cholinergic nervous system in geriatric depression . Significant cognitive and behavioral effects of scopolamine were observed only at the high dose ( 0.5 mg ) , while lower doses and lorazepam showed no significant differences from placebo .  Cognitive deficits caused by scopolamine were in the areas of new learning , access to semantic memory , vigilance , and continuous performance . Behavioral effects consisted of activation , restlessness , and anxiety , but there was no significant effect on depressed mood . These results suggest that elderly depressed patients with mild to moderate cognitive impairment seem to be more similar to previously studied elderly controls rather than to patients with Alzheimer 's disease in their reaction to short-term cholinergic blockade , and suggest that the cognitive and mood changes often seen in geriatric depression may involve factors other than disturbed muscarinic cholinergic mechanisms In seasickness , the central cholinergic-noradrenergic balance is disturbed . Capsules of identical appearance -- containing scopolamine hydrobromide 0.3 mg , scopolamine hydrobromide 0.3 mg + ephedrine hydrochloride 25 mg , or placebo -- were given prophylactically three times daily to 30 naval cadets during a crossing . In this r and omized , double-blind trial the superiority of scopolamine and scopolamine + ephedrine over placebo was confirmed . Ephedrine did not clearly increase the effectiveness of scopolamine .  One subject in the scopolamine group and one in the placebo group interrupted the treatment . The symptoms of seasickness as well as the number of side-effects of the drugs decreased on the third day of the study . Scopolamine alone or in combination with ephedrine proved useful in the prevention of seasickness in young healthy male volunteers Some antidepressant agents generate differential benefit based on gender . Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined . This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration . A total of 52 male and female out patients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind , r and omized , placebo-controlled , crossover clinical trial involving seven i.v . infusions of placebo or scopolamine ( 4 μg/kg ) . Following a single-blind placebo lead-in , participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence . Each block included three sessions . Clinical ratings were acquired before each infusion and included the Montgomery – Asberg Depression Rating Scale ( MADRS ) and the Hamilton Anxiety Rating Scale ( HAM-A ) . A treatment group × block interaction ( F=21.0 , p<0.001 ) was observed in MADRS scores across gender , and the reduction was significant by the evaluation following the first scopolamine administration ( F=8.4 , p=0.006 ) . The treatment group × block interaction was also significant in males ( F=3.8 , p=0.043 ) and females ( F=35.6 , p<0.001 ) separately . A block × gender interaction ( F=7.4 , p=0.009 ) indicated that the response magnitude was larger in women . The treatment × block interaction was significant for the HAM-A across gender ( F=12.0 , p<0.001 ) , and was significant for females ( F=24.9 , p<0.001 ) but not for males ( F=1.3 , p=0.30 ) . When comparing the baseline block to study end , the block × gender interaction ( F=12.6 , p=0.001 ) showed that the antianxiety response was greater in women . Men and women show a rapid antidepressant response  following scopolamine , but the magnitude of response is larger in women than in men In two placebo-controlled , double-blind , r and omized trials scopolamine ( 0.3 mg ) alone or combined with ephedrine ( 25 mg ) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory . Scopolamine was effective both alone and in combination with ephedrine , which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness . Ephedrine did not markedly increase the effectiveness of scopolamine . Side-effects were slight and did not disturb the operating ability of the volunteers In contrast to sleep studies of adult depressives that have consistently demonstrated abnormalities of sleep continuity , slow-wave sleep , and REM sleep , existing studies of depressed children and adolescents have been conflicting . Furthermore , only one study has explored the cholinergic regulation of sleep in early-onset depressives . In the present study , the electroencephalographic sleep of 20 adolescent out patients with major depressive episodes and 13 normal control adolescents was obtained on two separate 2-night sessions , 1 night incorporating challenge with scopolamine .  Depressed adolescents showed increased baseline phasic REM sleep measures , increased arousals , a trend toward reduced slow-wave sleep , and a greater difference in the change of first REM period density on the scopolamine night versus placebo night compared to controls . These findings support the continuity of some sleep abnormalities of depression into adolescence , and suggest that adolescent depression may be associated with alterations of cholinergic neurotransmission in some patients CONTEXT The need for improved therapeutic agents that more quickly and effectively treat depression is critical . In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide ( 4 microg/kg intravenously ) compared with placebo ( P = .002 ) . Subsequently a clinical trial was design ed to assess more specifically the antidepressant efficacy of scopolamine . OBJECTIVE To evaluate scopolamine as a potential antidepressant agent . DESIGN Two studies were conducted : a double-blind , placebo-controlled , dose-finding study followed by a double-blind , placebo-controlled , crossover clinical trial . SETTING The National Institute of Mental Health . Patients Currently depressed out patients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder . Of 39 eligible patients , 19 were r and omized and 18 completed the trial . INTERVENTIONS Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide ( 4 microg/kg ) . Individuals were r and omized to a placebo/scopolamine or scopolamine/placebo sequence ( series of 3 placebo sessions and series of 3 scopolamine sessions ) . Sessions occurred 3 to 5 days apart . MAIN OUTCOME MEASURES Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine . RESULTS The placebo/scopolamine group showed no significant change during placebo infusion vs baseline ; reductions in depression and anxiety rating scale scores ( P<.001 for both ) were observed after the administration of scopolamine compared with placebo . The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores ( P<.001 for both ) after the administration of scopolamine , relative to baseline , and these effects persisted as they received placebo . In both groups , improvement was significant at the first evaluation after scopolamine administration ( P < or = .002 ) . CONCLUSION Rapid , robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses BACKGROUND Panic attacks can be induced in persons with panic disorder by inhalation of carbon dioxide . Hypercapnia also elicits a reflex hyperventilation , which is controlled in part by cholinergic mechanisms . This study investigated whether the exaggerated response to carbon dioxide in panic disorder ( PD ) can be modulated by antagonists of muscarinic cholinergic receptors . METHODS Twelve patients with PD received biperiden hydrochloride ( a muscarinic antagonist that crosses the blood-brain barrier ) , pirenzepine hydrochloride ( a muscarinic antagonist that does not cross the blood-brain barrier ) , or placebo 2 hours before a 35 % carbon dioxide-65 % oxygen respiratory challenge ( vs air as a placebo ) on 3 separate days , in a double-blind , r and om crossover design . RESULTS According to patients ' self-ratings of subjective anxiety , inhalation of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo . After biperiden treatment , however , hypercapnia elicited a response profile similar to that elicited by air , whereby subjective anxiety remained similar to preinhalation levels . CONCLUSIONS Consistent with the hypothesis of the study , a central ly active muscarinic antagonist can block the response to carbon dioxide commonly observed in subjects with PD
Scopolamine is an effective and rapid antidepressant in both unipolar and bipolar depression , working as quickly as 3 days after initial infusion .
OBJECTIVES The cholinergic-adrenergic hypothesis of mania and depression states that depression is characterized by an increase in central cholinergic activity relative to noradrenergic tone .
Scopolamine is a central ly acting competitive inhibitor of the muscarinic cholinergic receptor site .
This review seeks to find all available data investigating scopolamine as an antidepressant .