Cognitive and Psychomotor Effects of Different Antidepressants in the Treatment of Old Age Depression

Siegfried, Klaudius; O'Connolly, M.

doi:10.1097/00004850-198607000-00006

Cited by 35 publications

(12 citation statements)

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“…These deficits might just be secondary to mood, but the idea that depression is accompanied by neuropsychological deficits independent of mood is gaining wider currency (Fleming et al, 2004). A link between 5-HT and memory deficits in depression is suggested by the fact that serotonergic antidepressants have been found to improve memory before mood improved (Allain et al, 1992;Fudge et al, 1990;Siegfried and O'Connolly, 1986). In our discussion of the ipsapirone study, we relied on the hypothesis that hypoactivity of 5-HT 1A receptors causes part or all of the memory deficits seen in depression.…”

Section: Discussionmentioning

confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT 1A and 5-HT 3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT 1A agonists ameliorate memory deficits in depression. INTRODUCTIONHypofunction of the 5-hydroxytryptamine (5-HT) system has emerged as a leading candidate cause for depression (Naughton et al, 2000;Middlemiss et al, 2002). At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999). This mirrors findings in depression, which is accompanied by moderate to severe memory deficits (Johnson and Magaro, 1987;Schaub et al, 2003). However, manipulations that increase 5-HT concentration or 5-HT receptor activation also lower memory performance, as indicated by receptor agonist studies in both humans (Riedel et al, 2002) and animals (Altman and Normile, 1988). Up to now, it is not known why both increased and decreased 5-HT activation have adverse effects on memory.5-HT binds to a large and disparate family of CNS receptors, which have effects that are sometimes opposite. Thus, many effects of different receptors seem to cancel each other out. In a review (see Supplementary Information on internet), we identify two robust effects of 5-HT in the hippocampus. First, 5-HT exerts a hyperpolarizing influence on principal cells; directly, via 5-HT 1A receptors, and indirectly, via facilitation of GABA release from local interneurons through 5-HT 3 receptors (Burnet et al, 1995;Piguet and Galvan, 1994). Activation of 5-HT 2A and 5-HT 2C receptors has been suggested to induce depolarization in principal cells (Piguet and Galvan, 1994;Barnes and Sharp, 1999), but these effects appear to be dominated by the depolarizing effects of 5-HT, as bath application of 5-HT will hyperpolarize principal cells in slice preparations of the dentate gyrus (Piguet and Galvan, 1994). In addition, through 5-HT 2C , 5-HT 4 , and 5-HT 7 receptors, afterhyperpolarizing (AHP) currents are downregulated, leading to reduced adaptation in principal cells (Torres et al, 1996;Bac...

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Section: Discussionmentioning

confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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“…Patients with depression and/or anxiety often express an obvious alteration in their psychomotor performance as well as their cognitive functions, such as attention, perception, memory and intellectual performance (Siegfried and O'Connolly 1986). In addition, side effects induced by psychotropic drugs may interfere with cognitive functions.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, side effects induced by psychotropic drugs may interfere with cognitive functions. It can be difficult for a patient treated with such drugs to state whether impaired function is related to the disease or is an effect of the drug (Siegfried and O'Connolly 1986). It is known that in depressive patients sedative antidepressants improve rather than impair psychomotor performance along with the amelioration of depression (Sepp/il/i et al 1978).…”

Section: Discussionmentioning

confidence: 99%

Objective and subjective assessments of the effects of flupentixol and benzodiazepines on human psychomotor performance

Mattila

Aranko

1988

Psychopharmacology

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The aim of this double-blind crossover trial was to compare the objective and subjective effects of flupentixol and lorazepam on human performance, and to reveal possible interactions between flupentixol and diazepam. Twelve healthy students received at 1-week intervals oral single doses of flupentixol 1 mg, flupentixol 2 mg, lorazepam 2.5 mg, placebo, and diazepam 15 mg alone and with flupentixol 1 mg. After the baseline measurements, the drugs were given in capsule form, and the tests were repeated 1.5, 3 and 4.5 h later. Diazepam was given at 1.5 h, to time its peak effect to coincide with that of lorazepam. Drug effects were measured objectively (two tracking tests, digit substitution, letter cancellation, flicker fusion, Maddox wing, tapping, memory) and subjectively (visual analogue scales, questionnaire). Blood samples were taken after each test time. Flupentixol 1 mg did not differ from placebo objectively or subjectively. Flupentixol 2 mg proved nearly inert objectively and on visual analogue scales. Lorazepam impaired objectively measured test performance, the clearest effects occurring at 3 and 4.5 h. It also impaired subjectively assessed performance. Diazepam impaired objective performance less than lorazepam, its effects peaking at 1.5 h after intake. Diazepam caused subjective drowsiness, clumsiness, mental slowness etc. as much as or more than lorazepam. The combination of 1 mg flupentixol and diazepam modified performance as much as diazepam alone. After the administration of 1 mg flupentixol, plasma concentrations were undetectable and levels after 2 mg were hardly detectable. Concentrations of lorazepam exceeded those of diazepam in direct bioassay, but they were much lower when bioassayed after solvent extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…All 19 RCTs that did not produce extractable response data found no differences between classes of antidepressants (Altamura et al, 1989a(Altamura et al, ,1989bAther et al, 1985;Biziere and Berger, 1990;Bloeink et al, 1985;De Ronchi et al, 1998;De Vanna et al, 1990;Dunner et al, 1992;Eklund et al, 1985;Feighner et al, 1988;Katona et al, 1999; La Pia , 1992;Mulsant et al, 2001;Pancheri et al, 1994;Pelicier and Schaeffer, 1993;Phanjoo et al, 1991;Rosenberg et al, 2007;Siegfried and O'Connolly, 1986;Smeraldi et al, 1998).…”

Section: Different Efficacy Between Classes Of Antidepressantsmentioning

confidence: 99%