The Effects of Venlafaxine on Autonomic Functions in Healthy Volunteers

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Fiedlerstrasse 27, Dresden, Germany.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 12/2007; 27(6):687-91. DOI: 10.1097/jcp.0b013e31815a255b
Source: PubMed


Antidepressants that block norepinephrine uptake may cause unwanted effects on autonomic functions such as reduction of heart rate variability. This randomized, double-blind, placebo-controlled study examined the effects of venlafaxine on heart rate variability, vasoconstrictory responses (VRs) of cutaneous blood vessels, and pupillary light reflex in humans. Twelve healthy male subjects aged 23 to 32 years (mean +/- SD, 26 +/- 3 years) orally received 37.5 mg of venlafaxine BID for 7 days and subsequently 75 mg BID for another 7 days. After a 14-day washout phase, placebo was administered to the subjects for 14 days under randomized double-blind crossover conditions. Heart rate variability was diminished, and the dilation phase of VR was prolonged during multiple dosing with venlafaxine (P < 0.05). A significant increase in resting pupil diameter, a decrease in amplitude, an increase in latency, and a shortening of the 33% recovery time of the pupillary light reflex were noted with the drug, whereas no changes were observed under placebo condition. Sustained VR and shortening of the recovery time of the pupillary light reflex are consistent with sympathetic potentiation resulting from noradrenaline reuptake blockade in cutaneous blood vessels and iris. The decrease in amplitude and increase in latency of the pupillary light reflex could be indicative of centrally mediated parasympathetic inhibition.

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    • "c measures as a function of central serotonergic activity in both treatment conditions . HRV effects of long - term SSRI administration have been investigated in various categories of patients . In depres - sion , in contrast to other antidepressant categories ( e . g . , tricyclic antidepressants , serotonin - norepinephrine reuptake inhibitors ; Siepmann et al . , 2007 ; Kemp et al . , 2010 ; Chang et al . , 2012 ) , SSRI treatment has been reported not to have a significant impact on resting HRV ( Rechlin , 1994 ; Straneva - Meuse et al . , 2004 ; Koschke et al . , 2009 ; Kemp et al . , 2010 , 2011 , 2014 ; Brunoni et al . , 2013 ; Hanson et al . , 2013 ) , although contradictory results have also be"
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    ABSTRACT: BACKGROUND: Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and thereby influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways including central autonomic pathways. However, only few studies assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV). METHODS: The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time and frequency domain HRV parameters assessed at both baseline and immediately after CCK-4 application. RESULTS: Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to HR (p < .001; pη2 = .499), SDNN (p < .001; pη2 = 576), RMSSD (p = .015; pη2 = 194), NN50(%) (p = .008; pη2 = .224), LF(%) (p = .014; pη2 = .196) and moderate effects with respect to HF(%) (p = .099; pη2 = .094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50(%), LF(%) and HF (%) than in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4 challenge compared to PLA. Secondary analysis indicated no effect of 5-HTTLPR polymorphism on CCK-4-induced autonomic response. Conclusions: Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.
    The International Journal of Neuropsychopharmacology 12/2014; 18(5). DOI:10.1093/ijnp/pyu053 · 4.01 Impact Factor
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    • "uction of variability in HR during recovery may have been due to the secondary effects of BP overshoot ; however , other studies have also found similar effects in their measure of HRV . A reduced HRV was found by Davidson et al . ( 2005 ) using paced breathing in their 3 - week study of up to 225 mg / day of venlafaxine XR in depressed patients . Siepmann et al . ( 2007 ) , in a sim - ilar 2 - week study of healthy volunteers taking up to 150 mg / day , also found reduced HRV . HRV is mainly under parasympathetic control , and reduced HRV is associated with impairment of parasympathetic function ( van Lieshout , 1989 ) ."
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    ABSTRACT: It is generally thought that venlafaxine raises blood pressure at higher doses; however, some studies have found no effect or a decrease in blood pressure. The aim of this study was to evaluate the cardiovascular (CV) effects of 3 weeks of dosing with venlafaxine, pregabalin and placebo on young healthy adults. Fifty-four participants, of mean age 23.1 years (sd 4.68), 29 male, were randomised into three parallel groups. Each group received one of the three drugs, dosed incrementally over a 3-week period to reach daily doses of 150 mg/day venlafaxine and 200 mg/day pregabalin. Blood pressure sphygmomanometer measurements, heart rate measurements, and orthostatic challenges recorded continuously beat-to-beat were performed weekly over this period and 5 days after treatment cessation. Results showed resting systolic blood pressure (SBP) and resting and standing diastolic blood pressure (DBP) and heart rate (HR) were significantly raised by venlafaxine compared with the pregabalin and placebo groups. SBP drop on standing was larger, the resulting overshoot was smaller, and recovery was slower on venlafaxine. HR recovery was significantly impaired by venlafaxine. CV changes were observed after only 1 week of dosing at 112.5 mg/day. These effects of venlafaxine are likely to be due to its action of noradrenergic reuptake inhibition. Copyright © 2013 John Wiley & Sons, Ltd.
    Human Psychopharmacology Clinical and Experimental 11/2013; 28(6). DOI:10.1002/hup.2346 · 2.19 Impact Factor
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    • "At the level of the iris, the latency to the light reflex and miotic response to light are thought to reflect parasympathetic activation (Heller et al. 1990; Loewenfeld 1999), whereas redilation is considered to mainly reflect sympathetic activation (Loewenfeld 1999; Morley et al. 1991). Notably, the parasympathetic input to the pupil may also be inhibited centrally via α 2 -adrenergic receptors in the Edinger–Westphal nucleus by an increase in sympathetic activity (Phillips et al. 2000a; Siepmann et al. 2007; Szabadi and Bradshaw 1996). Furthermore, the serotonin system has been shown to indirectly influence pupillary function, possibly by enhancing sympathetic activity (Prow et al. 1996). "
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    ABSTRACT: RATIONALE: Pupillometry can be used to characterize autonomic drug effects. OBJECTIVE: This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function. METHODS: Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design. RESULTS: MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function. CONCLUSIONS: The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.
    Psychopharmacology 06/2012; 224(3). DOI:10.1007/s00213-012-2761-6 · 3.88 Impact Factor
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