Advertisement

Psychopharmacology

, Volume 168, Issue 3, pp 293–298 | Cite as

Effects of sertraline on autonomic and cognitive functions in healthy volunteers

  • Martin SiepmannEmail author
  • Jens Grossmann
  • Michael Mück-Weymann
  • Wilhelm Kirch
Original Investigation

Abstract

Rationale

Though sertraline, a selective serotonin reuptake inhibitor (SSRI), causes autonomic and cognitive adverse events such as dry mouth and somnolence, there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature.

Objective

To compare the effects of sertraline on cognitive and autonomic functions with those of placebo in healthy humans.

Method

A randomized, double blind, cross over study of 12 healthy male volunteers aged 24 (21– 32; median; range) years. Subjects orally received 50 mg sertraline and placebo once daily for periods of 14 days each with at least 14 days in between. Heart rate variability (HRV), skin conductance level (SCL) and skin conductance response (SCR) following sudden deep respiration were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed repeatedly before the start of drug administration and on the last treatment day.

Results

Sertraline caused a significant reduction of heart rate and SCL (P<0.05), whereas HRV and SCR were not changed. Cognitive functions such as flicker fusion frequency, memory, choice reaction time and psychomotor performance were not influenced by sertraline but slow and fast beta power density in the qEEG was increased.

Conclusion

Cognitive and psychomotor performance are not altered in healthy humans receiving multiple dosing with sertraline. The observed decreases in heart rate and SCL may be due to a sympatho-inhibitory effect of sertraline.

Keywords

Sertraline Autonomic function Cognitive function qEEG 

Introduction

Cognitive impairment, psychomotor retardation and autonomic disturbances are among the characteristic features of clinical depression. The sedative and autonomic effects induced by antidepressants may be countertherapeutic, since they can exacerbate these aspects of the clinical profile. It was previously demonstrated that serotonin is critical in the regulation of cognitive and autonomic functions such as mood, aggressiveness, body temperature, heart rate and blood pressure (Fuller 1995). The naphthylamine derivative sertraline, a selective serotonin reuptake inhibitor (SSRI), inhibits 5-HT reuptake like other substances of its class. Compared to older antidepressants (TCAs), which affect multiple transmitters resulting in marked autonomic and cognitive disturbances, SSRIs target the serotonin system much more selectively. However, autonomic signs, i.e. symptomatic bradycardia, tachycardia, hypotension, dry mouth and dizziness have also been reported with SSRIs (Doogan 1991; Spigset 1999; Isbister et al. 2001). Serotonin plays a critical role in the regulation of autonomic functions (Grubb and Karas 1998). The brain`s control of sympathetic output appears to be closely linked with central serotonergic mechanisms. It was previously shown in a cat model that sympathetic neuroactivity can be significantly suppressed by increased release of brain serotonin, resulting in a reduced susceptibility to ventricular fibrillation (Lehnert et al. 1987). It may therefore be assumed that enhancement of brain serotonin induced by an SSRI alters autnomic functions. On the other hand, SSRIs are not entirely devoid of effects on other neurotransmitter systems (Bolden Watson and Richelson 1993), and these additional pharmacological activities may have an impact on their clinical profile. Parameters of heart rate variability and electrodermal reactivity can be employed to investigate autonomic functions in humans (Jacobs et al. 1994; Agelink et al. 2001; Mück-Weymann et al. 2001; Siepmann et al. 2001, 2002). Various CNS symptoms such as somnolence, agitation and tremor may be associated with sertraline and other SSRIs (Doogan 1991; Edwards and Anderson 1999). In the literature, there are only a few and inconclusive clinical trials on the cognitive effects of sertraline in healthy humans (Mattila et al. 1988; Kerr and Hindmarch 1996; Schmitt et al. 2001). To our knowledge, studies on the effects of sertraline on autonomic functions in healthy men have not been reported in the literature up to now. Therefore it was the aim of the present study to compare the effects of multiple dosing with sertraline on autonomic and cognitive functions with those of placebo in healthy male volunteers.

Materials and methods

Subjects

Twelve healthy male subjects, aged 24 (21–32; median; range) years, weighing 72 (61−79) kg and 179 (170–187) cm, in height were enrolled in the study. The subjects were included after a standard physical examination, routine clinical laboratory tests and a 12-lead ECG. The study was conducted according to the Declaration of Helsinki (Somerset West Amendment 1996) and German regulations. Written informed consent from the subjects and approval from the Hospital Ethics Committee (Dresden, Germany) were obtained.

Study procedure

No concomitant drug therapy was allowed for 2 weeks before and during the study period. The subjects were not allowed to smoke or to consume alcoholic or caffeine-containing beverages for 10  before and throughout the trial. Each subject received under randomized and double blind cross-over conditions capsules with 50 mg sertraline or placebo once daily for 14 days each. The capsules were taken orally by the subjects together with 100 ml water at 8.30 a.m. Treatment phases were separated by a wash out period of at least 14 days. Cognitive as well as psychomotor performance was tested at 0 (pretreatment), 5, 3, 5 and 8 h after the morning dose was given on the last treatment day. Assessment of skin conductance response (SCR), ECG and EEG recording were performed subsequently at corresponding time points. Room temperature was kept constant between 24 and 25°C. Blood pressure was monitored before start of medication as well as on treatment days 11 and 14, and subjects were asked if they had experienced any side effects throughout the study.

Heart rate variability

Heart rate analysis was carried out with the computer program Chart (AD Instruments, Castle Hill, Australia) as previously described (Siepmann et al. 2002). In brief, the ECG signal was digitized at a sample rate of 400 per second. Respiration was monitored by registration of chest movements. After a resting period of 10 min, subjects were instructed to breath deeply at a frequency of six cycles per minute (6 s inspiration, 4 s expiration) as deep respiration was demonstrated to produce maximal HRV in healthy volunteers (Mück-Weymann 2000). The root mean squares of successive differences of R-R intervals (RMSSD) were calculated from 200 artifact free beats. A spectral power analysis was carried out over 3 min recording by means of a fast Fourier transformation (FFT). Absolute power values were calculated for three frequency bands: very low frequency (VLF)=0.01–0.04 Hz, low frequency (LF)=0.04–0.15 Hz and high frequency (HF)=0.15–0.4 Hz.

Skin conductance response

The method has been described in detail elsewhere (Siepmann et al. 2001). Briefly, the skin conductance level (SCL) was measured in μSiemens (μS) from two medial phalanges with a Powerlab polygraph (AD Instruments). The maximum increase in amplitude following sudden deep respiration (SCR) was calculated to quantify the functional reactivity of sweat glands.

Quantitative EEG

The EEG signal (T3-A2 derivation) and electrooculogram were recorded for periods of 5 min each with the subjects keeping their eyes closed. The electrophysiological variables (notch filter at 50 Hz, 0.3 Hz calibration: 50 μV, 10 Hz sinus wave) were digitized at 250 Hz and stored on tape. After visual screening and exclusion of artifacts the EEG recordings were submitted to an FFT algorithm of 4 s epochs. Absolute spectral power density was assessed for six frequency ranges (delta 0.25–3.75 Hz, theta 4.00–7.75 Hz, alpha1 8.00–9.75 Hz, alpha2 10.00–12.75, beta1 13–17.75, beta2 18–32 Hz).

Psychometric tests

Psychometric testing was done with a computerized version of the Vienna Testsystem (Schuhfried, Mödling, Austria). Prior to each test, instructions were given to the subjects and subsequently a training session was performed. Subjects responded by touching fields on a computer screen with a light pen or turning knobs or pushing bottoms on a panel. Subjective mood was assessed with a 35-item version of the Profile of Mood States (POMS; Gibson 1997). Flicker fusion frequency is a means of measuring the ability to distinguish discrete sensory data. The frequency of flicker light emitted by a diode in foveal fixation was increased in an ascending mode until it was perceived by the subjects as constant light. Individual thresholds were then determined. The choice reaction time was measured with the Viennese Reaction Device. The subjects were presented yellow light, red light and a beep tone alone and in various combinations. They were instructed to react as fast as possible when yellow light and beep tone were presented simultaneously. Visual memory span was assessed with a computerized version of the Block Board tapping test (Smirni et al. 1983). Subjects had to reproduce tapping-sequences by pointing on blocks that were presented on the screen and tapped in a randomized order. When a subject failed to reproduce three consecutive sequences the test was interrupted. The maximum length of a sequence correctly replied (block span) was recorded. The two-hand coordination test was used to assess psychomotor ability. Subjects had to move a light dot along a given path. They were fed back with an acoustic signal when leaving the path. The time taken for the total path was recorded and the percent error time was calculated as the ratio of total error time to total time.

Statistical analysis

The statistical analysis of all data was performed with the Sigma Stat software package (Jandel, San Rafael, Calif., USA). The primary assessment variable was heart rate. Friedman repeated measures ANOVA on ranks was applied, as the values were not normally distributed. Individual comparisons of active treatment and placebo conditions were made using Student-Newman-Keuls post hoc tests with an a priori criterion of P<0.05.

Results

The effects of sertraline on heart rate and parameters of heart rate variability are summarized in Table 1. A significant decrease of heart rate was seen 0.5, 5 and 8 h after multiple dosing with sertraline when compared post hoc with pretreatment and placebo conditions. In contrast, parameters of heart rate variability such as RMSSD, and absolute power in the various frequency bands were not changed. No significant changes in systolic and diastolic blood pressure were noted. As it is pointed out in Table 2 skin conductance level (SCL) was significantly decreased 0.5 and 3 h following subchronic administration of sertraline, whereas SCR was not altered. Sertraline had no influence on choice reaction time, psychomotor coordination, memory span, flicker fusion frequency and mood (data not shown). Absolute power density was enhanced in the slow beta (beta1)and fast (beta2) ranges of the quantitatively analysed EEG 0.5, 3 and 5 hours following multiple dosing with sertraline (Table 3). Theta power was enhanced 3 h after the last dose was given. No changes in power density were seen in other frequency ranges of the qEEG.
Table 1.

Heart rate (HR; bpm), root mean square of successive differences of RR intervals (RMSSD; ms), absolute power in the very low (VLF), low (LF) and high frequency (HF) bands (ms2; median; range)

Time

Parameter

Sertraline

Placebo

0 h (pretreatment)

HR

66 (56–78)

65 (51–76)

RMSSD

77.0 (53.0–171.6)

89 (43.7–172.8)

VLF

289.8 (44.9–3020.1)

389.7 (72.0–1761.3)

LF

5428.5 (1729.9–15,046.6)

6579.3 (2114.4–24,747.4)

HF

476.6 (187.9–3063.9)

649.9 (67.1–1957.9)

1 h (last day)

HR

60 (50–67)*

62 (50–79)

RMSSD

76.4 (36.4–127.0)

105.9 (63.6–151.3)

VLF

454.7 (65.3–1674.8)

350.1 (142.1–6210.5)

LF

6073.8 (872.1–14,410.8)

8240.8 (3724.0–15,019.4)

HF

547.4 (121.6–1032.0)

1144.8 (353.8–2769.8)

3,5 h (last day)

HR

66 (54–74)

71 (55–80)

RMSSD

81.1 (52.1–156.9)

82.7 (45.5–151.0)

VLF

220.8 (31.4–958.9)

231.6 (23.3–1099.0)

LF

6192.4 (1671.8–10,793.1)

5557.3 (2016.8–15,384.9)

HF

551.8 (196.1–2719.6)

875.7 (295.4–2997.9)

5.5 h (last day)

HR

61 (51–71)*

65 (57–83)

RMSSD

91.3 (52.0–190.0)

98.9 (47.5–159.9)

VLF

414.0 (89.4–1742.0)

394.2 (71.8–6198.4)

LF

6508.5 (2210.6–17,271.0)

6912.3 (2763.0–13,422.8)

HF

570.7 (116.1–2887.6)

1054.2 (301.3–2464.1)

8.5 h (last day)

HR

64 (50–72)*

64 (58–80)

RMSSD

77.2 (44.7–176.6)

98.2 (52.8–153.8)

VLF

287.8 (96.5–1854.4)

281.7 (74.3–4032.6)

LF

5954.9 (2153.2–18,762.0)

7284.4 (3526.9–11,551.8)

HF

427.2 (172.0–3281.1)

824.3 (288.0–2654.0)

*P<0.05 when compared post hoc with pretreatment (hour 0) and with placebo

Table 2.

Skin conductance level (SCL) and skin conductance response (SCR; μSiemens; median; range)

Time

Parameter

Sertraline

Placebo

0 h (pretreatment)

SCL

29.6 (19.3–49.3)

33.5 (21.8–43.5)

SCR

8.5 (0.0–31.2)

8.0 (0.0–22.9)

1 h (last day)

SCL

25.0 (18.7–46.3)*

29.6 (20.9–53.2)

SCR

3.7 (0.0–31.4)

4.3 (0.0–17.9)

3.5 h (last day)

SCL

25.5 (18.9–35.6)*

28.3 (21.5–47.5)

SCR

2.4 (0.0–10.9)

3.2 (0.0–17.3)

5.5 h (last day)

SCL

28.4 (19.5–47.0)

32.6 (22.9–44.6)

SCR

5.6 (0.1–15.9)

4.8 (0.0–18.9)

8.5 h (last day)

SCL

30.5 (25.7–46.7)

33.1 (21.4–44.2)

SCR

5.7 (0.0–15.2)

8.2 (0.0–22.4)

*P<0.05 vs pretreatment (hour 0) and placebo

Table 3.

Quantitative EEG absolute power density (μV2/Hz; median; range)

Time

Frequency band

Sertraline

Placebo

0 h (pretreatment)

Delta

22.0 (11.8–61.8)

15.7 (9.1–52.5)

Theta

4.1 (2.1–8.4)

4.0 (2.0 –11.0)

Alpha1

12.9 (1.3–35.7)

11.4 (1.2–24.2)

Alpha2

6.2 (0.9–16.1)

4.6 (1.1–15.4)

Beta1

1.3 (0.4–2.6)

1.0 (0.6–2.6)

1.25 h (last day)

Delta

27.2 (9.7–103.7)

17.2 (8.3–37.0)

Theta

4.4 (2.4–11.1)

3.83 (2.15–11.1)

Alpha1

11.2 (1.4–37.0)

11.9 (1.4–31.1)

Alpha2

5.2 (1.0–13.3)

4.6 (1.0–16.9)

Beta1

1.4 (0.6–3.3)*

1.0 (0.5–3.0)

Beta2

0.5 (0.2–3.3)*

0.4 (0.2–1.1)

3.75 h (last day)

Delta

25.7 (10.1–95.0)

26.5 (8.5–56.2)

Theta

4.6 (2.3–11.5)*

4.8 (2.2–9.2)

Alpha1

14.8 (1.4–30.9)

9.3 (2.0–21.7)

Alpha2

6.1 (1.0–16.4)

3.3 (1.2–15.2)

Beta1

1.8 (0.6–3.7)*

1.0 (0.5–2.9)

Beta2

0.8 (0.2–4.3)*

0.3 (0.2–1.2)

5.75 h (last day)

Delta

24.4 (10.8–159.3)

22.2 (10.1–47.1)

Theta

5.0 (2.3–11.9)

4.8 (2.7–10.7)

Alpha1

13.5 (1.7–35.9)

11.8 (1.7–26.4)

Alpha2

6.5 (1.1–14.6)

5.0 (1.1–16.8)

Beta1

2.0 (0.6–3.6)*

1.1 (0.6–3.3)

Beta2

0.8 (0.2–4.3)*

0.4 (0.2–1.9)

8.75 h (last day)

Delta

22.3 (11.0–90.0)

16.5 (6.2–55.1)

Theta

4.4 (2.2–15.9)

5.3 (2.5–14.6)

Alpha1

11.7 (1.7–31.7)

12.5 (1.5–36.1)

Alpha2

6.8 (1.1–17.5)

5.1 (1.2–18.5)

Beta1

1.4 (0.5–3.4)

1.1 (0.6–3.9)

Beta2

0.6 (0.2–3.1)

0.4 (0.1–1.4)

*P<0.05 vs pretreatment (hour 0) and placebo

Six of our subjects spontaneously reported somnolence when receiving sertraline. Another six complained of headache and two reported difficulties in concentrating. Insomnia was seen with sertraline in three cases. Further adverse events are summarized in Table 4.
Table 4.

Adverse events reported by the subjects (n=12)

Adverse event

Sertraline

Placebo

Dry mouth

1

Somnolence

6

Dizziness

1

Insomnia

3

1

Lack of concentration

2

Head ache

6

1

Pruritus

1

Nausea

1

Pyrosis

2

Diarrhoea/loose stools

3

1

Prolonged ejaculation

1

Disturbed vision

1

Discussion

Autonomic functions

The role of serotonin in regulation of autononomic functions has become increasingly evident. It was previously demonstrated in cats that intracerebral ventricular injection of 5-hydroxytryptophan causes an abrupt decline in heart rate, blood pressure and sympathetic activity (Tadepalli et al. 1977). It was also shown that serotonin plays an important role in the renal sympathetic regulation in rats (Morgan et al. 1988). Cases of severe bradycardia were observed with sertraline as with other SSRIs (Feder 1991; Shapiro et al. 1999; Isbister 2001). A symptomatic decrease of systolic blood pressure was noted with paroxetine and fluoxetine (Rodriguez de la Torre et al. 2001). Further signs of autonomic dysfunction and excessive perspiration and urinary incontinence were described with SSRIs, including sertraline fluoxetine, paroxetine, fluvoxamine and citalopram (Masand and Gupta 1999; Votalato et al. 2000). Analysis of heart rate variability and SCR provides insight into autonomic functions. HRV parameters such as the RMSD and the HF band of spectral analysis are mainly controlled by action of the parasympathetic vagus nerve, whereas the results of the LF and VLF bands are essentially influenced by sympathetic activity (Kobayashi et al. 1999). Changes in electrical conduction of the skin incorporate both slow shift in SCL and more transient shifts, that is, SCR which have also been referred to as galvanic skin response (GSR; Dawson et al. 2000). SCL and SCR reflect activity within the sympathetic axis of the autonomous nervous system and it is noticeable that there is no parasympathetic innervation of sweat glands, although the activity is mediated by acetylcholine via m3-receptors (Low et al. 1992). In the present study, parameters of HRV and SCR were not altered but heart rate and SCL significantly decreased during multiple dosing with sertraline. Heart rate is under sympathetic and parasympathetic control. Sertraline, like most SSRIs, has no significant affinity for adrenergic (alpha1, alpha2, or beta) and muscarinergic receptors (MacQueen et al. 2001). Taking this into account, drug-induced decreases in heart rate and SCL would not be expected. However, in vivo experiments suggested that sustained serotonin reuptake inhibition decreases the firing rates of locus coerulus noreepinephrine neurons (Szabo and Blier 2002). It seems that the brain`s control of sympathetic output is closely linked with central serotonergic mechanisms (high serotonin, low sympathetic output, low serotonin, high sympathetic output). This concept fits well with the observation that patients suffering from depression after myocardial infarction are at a significantly higher risk for sudden death than their non-depressed counterparts (Lown and Verrier 1976). It is also in line with previous studies describing a heart rate lowering effect of SSRIs such as fluoxetine, paroxetine and citalopram (Roose et al. 1998; Rasmussen et al. 1999; Yeragani et al. 2002). Interestingly, it has been shown that sertraline treatment in patients suffering from major depression after acute myocardial infarction was associated with reduced ventricular ectopic activity and facilitation of recovery of cardiac autonomic function (Shapiro et al. 1999; McFarlane et al. 2001).

Cognitive functions

Sertraline not only inhibits serotonin but also dopamine reuptake (Bolden-Watson and Richelson 1993; Tasumi et al. 1997). There is evidence suggesting the involvement of dopamine in cognitive functions such as memory and motor action (Luiciana et al. 1998). Thus, one may postulate that sertraline improves cognitive and psychomotor performance. It was previously shown that subchronic administration of 50 and 100 mg sertaline improved single aspects of cognitive functions such as verbal fluency in healthy volunteers (Schmitt et al. 2001). In contrast, it was demonstrated that single doses of 200 and 400 mg sertraline had detrimental effects on psychometric test performance in healthy subjects (Saletu et al. 1986; Saletu and Grunbereger 1988). The present study indicates that sertraline does not influence cognitive functions such as vigilance, choice reaction, memory and psychomotor coordination when given subchronically at daily doses of 50 mg to healthy young subjects. This is in accordance with previous trials in elderly healthy volunteers who received 100 mg sertraline as single doses (aged 50–67 years; Mattila et al. 1988; Kerr and Hindmarch 1996). In the present study, nine of 12 subjects spontaneously reported somnolence and/or lack of concentration when receiving multiple doses with sertraline.

qEEG

The observed enhancement of slow and fast beta power in the qEEG hints at sublinical sedation, as augmentation of beta activity has consistently been described as part of the qEEG profile of sedative antidepressants such as amitripytline (Saletu et al. 1983; Yamadera et al. 1987). Our results are in line with a previous study demonstrating an increase in beta power with single doses of 200 and 400 mg sertraline in healthy young volunteers (Saletu et al. 1986).

Conclusions

The present results suggest that sertraline does not interfere with cognitive and psychomotor abilities when given subchronically at therapeutic doses. Heart rate and skin conductance level decreased during multiple dosing with sertraline, which may be due to a central sympatho-inhibitory effect of the substance. The clinical implications of these findings remain to be determined in long-term studies.

Notes

Acknowledgements

This work was part of a thesis. The authors are sincerely thankful to Mrs. E. Hempel for her assistance in conducting the study.

References

  1. Agelink MW, Mayewsky T, Andrich J, Mück-Weymann M (2002) Short term effects of intravenous bezodiazepines on autonomic neurocardiac regulation: a comparison between midazolam, diazepam and lorazepam. Crit Care Med 30:997–1006PubMedGoogle Scholar
  2. Bolden-Watson C, Richelson E (1993) Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 52:1023–1029PubMedGoogle Scholar
  3. Dawson ME, Schell AM, Filion DL (2000) The electrodermal system. In: Cacioppo JT, Tassinary LG, Berntson GC (eds) Handbook of psychophysiology. Cambridge University Press, Cambridge, pp 200–223Google Scholar
  4. Doogan DP (1991) Toleration and safety of sertraline: experience worldwide. Int Clin Psychopharmacol 6:47–56PubMedGoogle Scholar
  5. Edwards JG, Anderson I (1999) Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs 57:507–533PubMedGoogle Scholar
  6. Feder R (1991) Bradycardia and syncope induced by fluoxetine. J Clin Psychiatry 52:138–139Google Scholar
  7. Fuller RW (1995) Neural functions of serotonin. Sci Am Sci Med 4:48–57Google Scholar
  8. Gibson SJ (1997) The measurement of mood states in older adults. J Gerontol Psychol Sci 52B:P167–P174Google Scholar
  9. Grubb BP, Karas BJ (1998) The potential role of serotonin in the pathogenesis of neurocardiogenic syncope and related autonomic disturbances. J Interv Electrophysiol 2:352–332Google Scholar
  10. Isbister GK, Prior FH, Foy A (2001) Citalopram-induced bradycardia and presyncope. Ann Pharmacother 35:1552–1555CrossRefPubMedGoogle Scholar
  11. Jacobs SC, Friedman R, Parker JD, Tofler GH, Jimenez AH, Muller JE, Benson H, Stone PH (1994) Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research. Am Heart J 128:1170–1177PubMedGoogle Scholar
  12. Kerr JS, Hindmarch I (1996) Citalopram and other antidepressants: comparative effects on cognitive function and psychomotor performance. J Serotonin Res 3:123–129Google Scholar
  13. Kobayashi H, Ishibashi K, Noguchi H (1999) Heart rate variability; an index for monitoring and analyzing human autonomic activities. Appl Hum Sci 18:53–59Google Scholar
  14. Lehnert H, Lombardi F, Raeder EA, Lorenzo AV, Verrier RL, Lown B, Wurtman RJ (1987) Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat. J Cardiovasc Pharmacol 10:389–397PubMedGoogle Scholar
  15. Low PA, Opfer-Gehrking TL, Kihara M (1992) In vivo studies on receptor pharmacology of the human eccrine sweat gland. Clin Autonom Res 2:29–34Google Scholar
  16. Lown B, Verrier RL (1976) Neural activity and ventricular fibrillation. N Engl J Med 294:1165–1170PubMedGoogle Scholar
  17. Luciana M, Collins PF, Depue RA (1998) Opposing roles for dopamine and serotonin in the modulation of human spatial working memory function. Cereb Cortex 8:218–226PubMedGoogle Scholar
  18. MacQueen G, Born L, Steiner M (2001) The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. CNS Drug Rev 7:1–24PubMedGoogle Scholar
  19. Masand PS, Gupta S (1999) Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry 7:69–84PubMedGoogle Scholar
  20. Mattila MJ, Saarialho-Kere U, Mattila M (1988) Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry 49:52–58PubMedGoogle Scholar
  21. McFarlane A, Kamath MV, Fallen EL, Malcolm V, Cherian F, Norman G (2001) Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. Am Heart J 142:617–623CrossRefPubMedGoogle Scholar
  22. Morgan DA, Thoren P, Wilczynski E, Victor RG, Mark AL (1988) Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats. Am J Physiol 255:H496–502PubMedGoogle Scholar
  23. Mück-Weymann M (2000) Methoden und Technik [Methods and techniques]. In: Mück-Weymann M (ed) Autonome Funktionskreise in Psychosomatik und Psychiatrie. Nicht-invasives Biomonitoring in der Psychopharmakotherapie. [Autonomic functions in psychosomatic medicine and psychiatry. Non-invasive monitoring of psychopharmacological therapy]. Hans Jacobs, Lage, pp 28–38Google Scholar
  24. Mück-Weymann M, Acker J, Agelink M (2001) Autonomic responses of blood vessels and sweat glands in patients with schizophrenia treated with olanzapine or clozapine. Psychopharmacology 157:368–372CrossRefPubMedGoogle Scholar
  25. Rasmussen SL, Overo KF, Tanghoj P (1999) Cardiac safety of citalopram: prospective trials and retrospective analyses. J Clin Psychopharmacol 19:407–415Google Scholar
  26. Rodriguez de la Torre B, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, Luderitz B, Rao ML (2001) Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Ther Drug Monit 23:435–440CrossRefPubMedGoogle Scholar
  27. Roose SP, Glassman AH, Attia E, Woodring S, Giardina EG, Bigger JT Jr (1998) Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 155:660–665PubMedGoogle Scholar
  28. Saletu B, Grunberger J (1988) Drug profiling by computed electroencephalography and brain maps, with special consideration of sertraline and its psychometric effects. J Clin Psychiatry 49:59–71PubMedGoogle Scholar
  29. Saletu B, Grünberger J, Rajna P (1983) Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine. Br J Clin Pharmacol 15:369S–384SGoogle Scholar
  30. Saletu B, Grunberger J, Linzmayer L (1986) On central effects of serotonin re-uptake inhibitors: quantitative EEG and psychometric studies with sertraline and zimeldine. J Neural Transm 67:241–266PubMedGoogle Scholar
  31. Schmitt JAJ, Kruizinga MJ, Riedel WJ (2001) Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. J Psychopharmacol 15:73–179Google Scholar
  32. Shapiro PA, Lesperance F, Frasure-Smith N et al. (1999) An open label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT trial). Am Heart J 137:1100–1106PubMedGoogle Scholar
  33. Siepmann M, Mück-Weymann M, Joraschky P, Kirch W (2001) The effects of reboxetine on autonomic and cognitive functions in healthy volunteers. Psychopharmacology 157:202–207PubMedGoogle Scholar
  34. Siepmann M, Krause S, Joraschky P, Mück-Weymann M, Kirch W (2002) The effects of St John`s wort extract on heart variability, cognitive functions and quantitative EEG—a comparison with amitriptyline and placebo in healthy men. Br J Clin Pharmacol 54:277–282CrossRefPubMedGoogle Scholar
  35. Smirni P, Villardita C, Tappala G (1983) Influence of different paths on spatial memory performance in the block-tapping test. Clin Neuropsychol 5:355–359Google Scholar
  36. Spigset O (1999) Adverse reactions of selective serotonin reuptake inhibitors: reports from a spontaneous reporting system. Drug Safety 20:277–287PubMedGoogle Scholar
  37. Szabo ST, Blier P (2002) Effects of serotonin (5-hydroxytryptamine, 5HT) reuptake inhibition plus 5-HT (2A) receptor antagonism on the firing activity of norepinephrine neurons. J Pharmacol Exp Ther 302:983–991CrossRefPubMedGoogle Scholar
  38. Tadepalli AS, Mills E, Schanberg SM (1977) Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain. J Pharmacol Exp Ther 202:310–319PubMedGoogle Scholar
  39. Tatsumi M, Groshan K, Blakely RD, Richelson E (1997) Pharmacological profile of antidepressants and related compounds at human monoamine transporters Eur J Pharmacol 340:249–258Google Scholar
  40. Votolato NA, Stern S, Caputo RM (2000) Serotonergic antidepressants and urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 11:386–388CrossRefPubMedGoogle Scholar
  41. Yamadera H, Ferber G, Matejcek M, Pokorny R (1987) Quantitative pharmaco-electroencephalographic differentiation between the CNS effects of bromocriptine and imipramine, drugs with qualitatively different antidepressant properties. Pharmacopsychiatry 20:54–59Google Scholar
  42. Yeragani VK, Pesce V, Jayaraman A, Roose S (2002) Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures. Biol Psychiatry 52:418–429CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Martin Siepmann
    • 1
    Email author
  • Jens Grossmann
    • 1
  • Michael Mück-Weymann
    • 2
    • 3
  • Wilhelm Kirch
    • 1
  1. 1.Institute of Clinical Pharmacology, Medical FacultyTechnical UniversityDresdenGermany
  2. 2.Clinic for Psychosomatic Medicine and Psychotherapy, Medical SchoolTechnical UniversityDresdenGermany
  3. 3.Institute of Molecular and Cellular PhysiologyFriedrich-Alexander-UniversityErlangenGermany

Personalised recommendations