Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Baseline mood-state measures as predictors of antidepressant response to scopolamine The "switch process" in manic-depressive illness. II. Relationship to catecholamines, REM sleep, and drugs. The effects of acute scopolamine in geriatric depression. Replication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial Differential prediction of first clinical response to serotonergic and noradrenergic antidepressants using the loudness dependence of auditory evoked potentials in patients with major depressive disorder. Differential effects of serotonergic and noradrenergic antidepressants on brain activity during a cognitive control task and neurofunctional prediction of treatment outcome in patients with depression. (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD). Serotonergic and Noradrenergic Modulation of Emotion Processing by Single Dose Antidepressants A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant Tricyclic antidepressants and tryptophan in unipolar depression. Sleep electroencephalographic abnormalities in adolescent depressives: Effects of scopolamine The Serotonergic Hypothesis for Depression in Parkinson's Disease: an Experimental Approach Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. Combined catecholamine and indoleamine depletion following response to ECT. Allopurinol for mania: a randomized trial of allopurinol versus placebo as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder. The switch mechanism and the bipolar/unipolar dichotomy.
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 Identifying predictors of antidepressant response will facilitate the successful treatment of patients suffering from depression .  Scopolamine produces robust antidepressant responses in unipolar and bipolar depression . Here we evaluate the potential for baseline self-ratings to predict treatment response to scopolamine .  Fifty-one unipolar and bipolar patients participated in a double-blind , placebo-controlled crossover trial . Following a single-blind placebo session , participants r and omly received P/S or S/P ( P=3 placebo ; S=3 scopolamine ( 4μg/kg ) sessions ) . Mood-state self-ratings ( Profile of Mood State ( POMS ) and Visual Analog Scales ( VAS ) ) and depression severity ( Montgomery-Åsberg Depression Rating Scale ( MADRS ) ) were obtained before each infusion . Day 1 ( baseline/placebo ) self-ratings were used in a discriminant function analysis to identify linear combinations of individual items that predict response . The discriminant analysis significantly separated responders from non-responders in both the unipolar and bipolar diagnostic subgroups . The discriminant functions accurately classified over 85 % of patients as responders/non-responders . The POMS depression subscale significantly correlated with clinical response , as did the VAS restlessness , sad , and irritated scales . These results indicate that self-report mood-ratings obtained before treatment can predict response outcome to scopolamine , and suggest that a constellation of mood-state features may be related to clinical response The data reported in this paper support the hypothesis that the neurotransmitter catecholamines ( dopamine and /or norepinephrine ) are functionally increased prior to the switch from depression into mania . Urinary norepinephrine was significantly elevated on the day prior to and during the manic episodes . Overall sleep and rapid eye movement were both decreased prior to and during the switch into mania in a few patients . Our pharmacological data is also supportive of this hypothesis . Brief administration of tricyclic medication has been associated with rapid switches from depression into mania . Large doses of levodopa ( which increases brain dopamine ) were regularly associated with brief hypomanic episodes in patients with past histories of mania . On the other h and , αmethyl-ρtyrosine , which inhibits the synthesis of norepinephrine and dopamine , was associated with a transitory switch out of mania in a few patients 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 BACKGROUND We previously reported that intravenous ( IV ) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives . The present study aim ed to replicate this finding in an independent sample limited to unipolar depressives . METHODS Out patients with major depressive disorder ( MDD ; n = 23 ; 22 were included in analyses ) participated in a double-blind , placebo-controlled , crossover trial . Subjects were r and omized into either a P/S or S/P sequence ( P = block of three placebo sessions ; S = block of three scopolamine sessions ; [ 4.0 microg/kg IV ] ) . Sessions occurred 3 to 5 days apart , such that time spent in each block lasted 1.5 to 2 weeks and the interval between blocks was 3 to 5 days . The Montgomery-Asberg Depression Rating Scale ( MADRS ) served as the primary outcome measure . RESULTS Following the initial block , the group receiving scopolamine first ( S/P ) showed a 32 % reduction in MADRS scores ( p < .001 ) , which exceeded the corresponding change of 6.5 % under placebo ( P/S ; p = .009 ) , confirming the a-priori hypothesis . Improvement was significant at the first evaluation that followed scopolamine administration ( p = .011 ) . In Block 2 , the P/S group showed a 53 % reduction in MADRS scores ( p = .001 ) following scopolamine versus placebo , whereas the reduction seen in S/P subjects who received scopolamine during Block 1 persisted as they received placebo during Block 2 . Scopolamine induced drowsiness , blurred vision , dry mouth , light-headedness , and reduced blood pressure , which were sufficiently well tolerated that no subject dropped out because of side effects . CONCLUSIONS These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response OBJECTIVE Predictors of treatment response to serotonergic versus nonserotonergic , e.g. , noradrenergic , antidepressants are of considerable clinical relevance as they could help to reduce the occurrence of patients ' receiving weeks or even months of unsuccessful treatment . Several studies show that the response to selective serotonin reuptake inhibitors can be successfully predicted by using the loudness dependence of auditory evoked potentials ( LDAEP ) , which denotes change in the amplitudes in response to different stimulus intensities and is to date one of the best vali date d indicators of the central serotonergic system . The aim of the current r and omized prospect i ve study was to investigate whether or not LDAEP also allows the differential prediction of treatment response to serotonergic versus noradrenergic antidepressants . METHOD Electrophysiologic recordings were performed on 48 subjects between 1999 and 2001 . After exclusions due to artifacts , the study sample consisted of 35 unmedicated in patients with a DSM-IV or ICD-10 diagnosis of major depressive disorder ( mean + /- SD age = 42.5 + /- 10.8 years ; 13 male , 22 female ; mean + /- SD score of 28.9 + /- 5.7 on the Hamilton Rating Scale for Depression [ HAM-D ] , the primary measure for psychopathology ) . The patients were then treated for 4 weeks with either the selective serotonin reuptake inhibitor citalopram or the noradrenaline reuptake inhibitor reboxetine . RESULTS Analysis of variance ( F = 5.05 , df = 1,31 ; p = .03 ) revealed that responders ( 50 % improvement in HAM-D score ) to the citalopram treatment were characterized by a strong LDAEP at baseline , and responders to reboxetine were characterized by a weak LDAEP at baseline . Non-responders to citalopram or reboxetine showed the inverse LDAEP characteristics , respectively . CONCLUSION This study is one of the first to demonstrate differential prediction of response to different classes of antidepressants . Patients at the beginning of an antidepressant treatment who show an initially strong LDAEP have a greater probability of responding to a serotonin-agonist antidepressant , whereas patients with a weak LDAEP will probably benefit more from a nonserotonergic , e.g. , noradrenergic , antidepressant . If these results were replicated in a larger sample , this simple electroencephalographic method could be more broadly used in clinical practice to support clinicians in replacing the trial and error method with a more targeted and individualized approach to antidepressant treatment BACKGROUND We investigated the differential effects of serotonergic and noradrenergic antidepressants on brain activation in patients with major depressive disorder during a Stroop task . We predicted that pretreatment hyperactivity in the rostral anterior cingulate cortex would predict better treatment outcomes . METHODS In total , 20 patients underwent naturalistic open-label clinical treatment with citalopram ( n = 12 ) or reboxetine ( n = 8) . We performed functional magnetic resonance imaging at baseline and after 6 weeks of treatment . RESULTS There were no significant group differences in clinical characteristics , treatment outcomes or baseline fMRI activations . The group by time interaction revealed significant voxels in the right amygdala-hippocampus complex ( p < 0.05 , family-wise error corrected by use of the bilateral amygdala and hippocampus mask image as a small volume ) , indicating a posttreatment blood oxygen level- dependent signal decrease in the citalopram group . Pretreatment hyperactivity in the rostral anterior cingulate cortex was not related to symptom improvement . LIMITATIONS Our study was a nonr and omized clinical trial . CONCLUSION These results indicate that serotonergic and noradrenergic antidepressants have a differential effect on brain activity , especially in the amygdala and hippocampus Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure ​(Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214  , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited Serotonergic and noradrenergic pathways are the main targets of antidepressants . Their differential effects on emotion processing-related brain activation are , however , to be further characterized . We aim ed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task , which was earlier shown to be associated with depressiveness . In a single-blind pseudo-r and omized crossover study , 21 healthy subjects ( 16 subjects finally included in the analysis ) participated to ingest a single dose at three time points of either 40 mg citalopram , a selective serotonin-reuptake inhibitor , 8 mg reboxetine , a selective noradrenaline-reuptake inhibitor , or placebo 2–3 h before functional magnetic resonance imaging ( fMRI ) . During fMRI , subjects performed a task comprising the anticipation and perception of pictures of either ‘ known ’ ( positive , negative , neutral ) or ‘ unknown ’ valence ( r and omly 50 % positive or negative ) . In direct comparison with citalopram and with placebo , reboxetine increased brain activity in the medial thalamus . Citalopram modulated certain prefrontal and insular areas more prominently . Other frontal and parieto-occipital areas were modulated by both drugs . In conclusion , the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas , and a prefrontal and insular focus of serotonergic modulation . These findings could have implication s for future selection criteria concerning personalized antidepressant medication in depression The noradrenaline ( NA ) hypothesis of depression is founded primarily on pre clinical and clinical ly indirect evidence . In two three-compartment r and omized parallel clinical trials conducted serially , we examined the significance of NA uptake for antidepressant activity . The racemic compound oxaprotiline ( hydroxymaprotiline ) is a highly specific inhibitor of NA uptake , whereas its R-(- ) enantiomer levoprotiline is totally devoid of this property . Oxaprotiline significantly resembled amitriptyline in its antidepressant potential . Conversely , levoprotiline significantly resembled placebo in antidepressant potential . Therefore , NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant Depressed patients ( unipolar ) were given one of the following combinations in an attempt to test aspects of the ' amine hypothesis ' and to find a preferential therapy : ( 1 ) clomipramine ; ( 2 ) clomipramine and tryptophan ; ( 3 ) desipramine and clomipramine , and ( 4 ) desipramine and tryptophan . Treatment ( 2 ) should have given optimal potentiation of 5-HT neurones and ( 3 ) and ( 4 ) should have acted similarly on both serotoninergic and adrenergic pathways . In no group was there any evidence of accelerated recovery , indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis 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 The serotonergic hypothesis for depression in Parkinson 's disease ( PD ) states that the reduced cerebral serotonergic activity that occurs in PD constitutes a biological risk factor for depression . The aim of our study was to assess the serotonergic hypothesis of depression in PD patients using an experimental approach . In a double-blind , r and omized order , placebo-controlled crossover design , the response on the Profile of Mood States ( POMS ) question naire to acute tryptophan depletion ( ATD ) was studied in 15 PD nondepressed patients and 15 control subjects , without a prior personal or family history of depression . PD patients had lower ( worse ) baseline scores on the sadness , fatigue and vigor subscales of the POMS , in both ATD and the placebo condition , but not on the tension and anger subscales . There was however neither a significe between group effect , nor significe within-group effect due to ATD . We could find no evidence of a specific serotonergic vulnerability of PD patients for depression . Therefore , our results do not support the serotonergic hypothesis for depression in PD OBJECTIVE To evaluate the antidepressant effect of oral scopolamine as an adjunct to citalopram . METHOD In this r and omized double-blind placebo-controlled study , patients were assessed in the outpatient clinics of 2 large hospitals from November 2011 to January 2012 . Forty patients ( 18 - 55 years ) with major depressive disorder ( DSM-IV-TR criteria ) and 17-Item Hamilton Depression Rating Scale ( HDRS ) score ≥ 22 were r and omly assigned to scopolamine hydrobromide ( 1 mg/d ) ( n = 20 ) or placebo ( n = 20 ) in addition to citalopram for 6 weeks . HDRS score was measured at baseline and days 4 , 7 , 14 , 28 , and 42 . The primary outcome measure was HDRS score change from baseline to week 6 in the scopolamine group versus the placebo group . Response was defined as ≥ 50 % decrease in HDRS score ; remission , as HDRS score ≤ 7 . RESULTS Augmentation with scopolamine was significantly more effective than placebo ( F(1,38 ) = 5.831 , P = .021 ) . Patients receiving scopolamine showed higher rates of response ( 65 % , 13/20 at week 4 ) and remission ( 65 % , 13/20 at week 6 ) than the placebo group ( 30 % , 6/20 and 20 % , 4/20 , respectively ; P = .027 , P = .004 , respectively ) . Patients in the scopolamine group showed higher rates of dry mouth , blurred vision , and dizziness than the placebo group . CONCLUSIONS Oral scopolamine is a safe and effective adjunct for treatment of patients with moderate to severe major depressive disorder . TRIAL REGISTRATION Iranian Registry of Clinical Trials identifier : I RCT 201201181556N31 The mechanism of action of electroconvulsive therapy ( ECT ) in treating major depression is unknown . We studied two c and i date mechanisms through inhibiting simultaneously the synthesis of noradrenaline and serotonin in patients immediately after successful treatment with ECT  using a r and omised , placebo-controlled , double-blind crossover design . There were no significant changes in depression scores under any experimental conditions , or between the amine-depleted and placebo groups despite reductions of 61 % in serum homovanillic acid , 47 % in 3-methoxy-4-hydroxyenylethyleneglycol , and 89 % in serum tryptophan . Catecholamine and serotonin availability may not be necessary for maintaining the initial antidepressant response to ECT OBJECTIVE An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders . Adenosine agonists have been shown to have properties similar to those of dopamine antagonists ; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum , and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors . Allopurinol increases adenosine levels in the brain , and hence is hypothesized to reduce the symptoms of mania . Two r and omized , placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale ( YMRS ) scores for drug compared to placebo , while a more recent , relatively small , add-on study showed negative results . Based on these data , our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and /or antipsychotic agents in manic patients with bipolar disorder . METHODS We performed a large , well-powered , multicenter , six-week , r and omized , placebo-controlled trial of allopurinol added to mood stabilizers and /or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode . RESULTS Both groups showed improvement on the YMRS ( effect size of 1.5 for placebo and 1.6 for allopurinol ) , with no difference observed between groups on YMRS scores ( t = 0.28 , p = 0.78 ) . There was no difference in the proportion of patients who responded to treatment ( defined as showing at least 50 % improvement in YMRS score ) between the two groups ( p = 0.92 ) , or in dropout rates ( p = 0.84 ) . LIMITATIONS None of our patients received lithium . However , the side effects of lithium and its narrow therapeutic index made the use of lithium less common and , therefore , our study results reflect common current clinical practice . In the present study , we used a variety of antipsychotic and /or mood stabilizing treatments , to which we added allopurinol ; one might hypothesize that add-on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers . CONCLUSIONS The findings of this large , well-powered study do not support add-on allopurinol as a treatment for acute mania . This study did not test the efficacy of allopurinol as monotherapy During open trials of intravenous and oral S-adenosyl methionine ( SAM ) and a placebo-controlled trial of intravenous SAM in 29 patients , 25 patients had SAM and four had placebo ( 27 courses of SAM , two of the patients receiving two trials a piece ) . Nine of 11 bipolar patients ( all SAM-treated ) switched into elevated mood state ( hypomania , mania and euphoria ) and two did not respond . Six endogenous unipolar patients improved and five did not . No non-endogenous patient or placebo patient responded for more than 14 days . No unipolar patient switched into elated mood . In eleven ( 38 % ) trials and nine ( 33 % ) patients there was a switch from depression to elation . Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored
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 .