Psychopharmacology

Los alucinógenos, el cerebro y la mente

by Carlos Manuel Quirce Balma

El presente trabajo intenta establecer el difícil puente entre la
psicofarmacología antropológica, religiosa y... more El presente trabajo intenta establecer el difícil puente entre la
psicofarmacología antropológica, religiosa y botánica; a la vez desglosa los mecanismos conocidos de acción de varias drogas psicodélicas. Una clasificación tri-partita de drogas que alteran la conciencia es expuesta y se logra aclarar diferencias entre los mecanismos de la acción neurocerebral de cada una hasta donde es posible científicamente hoy día. Mucha de la información proviene también del estudio del chamanismo suramericano y
norteamericano. Algunos trabajos psicofarmacológicos al respecto de la brujería europea son incluídos.

Recientes adelantos en el área del estrés: los últimos veinticinco años

by Carlos Manuel Quirce Balma

The present paper attempts to bridge a period
of approximately twenty years of basic and
applied research in... more The present paper attempts to bridge a period
of approximately twenty years of basic and
applied research in the área of stress. Emphasis
has been laid upon the behavioral,
psychobiological and psychopharmacological
variables thathavecharacterized the more
updated work in the field. The implications of
models derived from genetic, biohormonal and
brain amine research are discussed with
emphasis upon the formulation of newer
models and paradigms of stress. A great deal
of weight has been placed on research that
links alcoholism to stress as well as to
addiction to central stimulants. Novel work on
morphine tolerance and the stress of social
violence is similarly discussed. The basic
contrast between psychobiological research
and psychosocial research in the field
constitutes an integral part of the paper.

Assessment of Brain Monoaminergic Signaling through Mathematical Modeling of Skin Conductance Response

by Sasa Brankovic

Chapter in "Neuroscience - Dealing with Frontiers", Editor: Carlos M. Contreras, InTech, 2012, pp. 83-108.

Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

by Nora S Vyas

Nora S. Vyas, Nitin Gogtay (2012)

Frontiers Psychiatry, Vol 3 (Article 29), 1-5
doi:10.3389/fpsyt2012.00029

Early onset schizophrenia (onset before adulthood) is a rare, severe and chronic form of schizophrenia. The clinical... more Early onset schizophrenia (onset before adulthood) is a rare, severe and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment refractory cses. Based on the current literature, second generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies.

O’Donnell, P. J. (2008, March). Drug promotion and prescribing trends. The Clinical Practitioner, 3(3), 3-6.

by peter o'donnell

Baseline severity of depression predicts antidepressant drug response relative to escitalopram

by Thomas E. Schlaepfer

Lamoure J., Stovel J. Varenicline and Suicidal Ideations. How Common is It?. Cdn J of CME 2012; 24(2): 14

by Dr. Joel Lamoure

Lamoure J., Stovel J. Varenicline and Suicidal Ideations. How Common is It?. Cdn J of CME 2012; 24(2): 14
Dr Joel Lamoure

In Canada, varenicline is currently indicated for smoking cessation in conjunction with counselling.1 There have been... more In Canada, varenicline is currently indicated for smoking cessation in conjunction with counselling.1 There have been numerous reports of increased suicidal ideation in patients taking varenicline, and in patients that are quitting smok- ing. This has resulted in the Health Canada Advisory warning health- care providers about the increased risk of serious neuropsychiatric adverse events in those patients taking varenicline. Specifically, depressed mood, agitation, hostili- ty, changes in behaviour, suicidal ideation and suicide, as well as worsening of pre-existing psychi- atric illness have been observed.2 This scenario is very reminiscent for me of the mid 1980’s when fluoxe- tine was first launched in the USA.

Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers

by Silke Conen

Conen S, Theunissen EL, Van Oers AC, Valiente R, Ramaekers JG.
J Psychopharmacol. 2011 Nov;25(11):1517-23.

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no... more Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two particpants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

Short-Term Effects of Morning Versus Evening Dose of Hydroxyzine 50 mg on Cognition in Healthy Volunteers

by Silke Conen

Conen S, Theunissen EL, Vermeeren A, Ramaekers JG.
J Clin Psychopharmacol. 2011 Jun;31(3):294-301.

It is well known that the sedative properties of antihistamines can differ considerably between individual drugs.... more It is well known that the sedative properties of antihistamines can differ considerably between individual drugs. Several factors have been suggested to determine the presence, absence, and/or magnitude of sedation by antihistamines. Research has suggested that the sedative effects caused by central H1 blockade partly depend on the availability of histamine competing for the same receptor and that this competition is affected by a mechanism related to sleep. Consequently, the present study was designed to compare the effects of evening and morning doses of the first-generation antihistamine hydroxyzine on cognition. It was expected that the sedative effect of hydroxyzine would be apparent in the evening after an evening dose but would be smaller in the morning after a morning dose owing to the greater release of histamine shortly after awakening. Eighteen participants (9 females) participated in a placebo-controlled, randomized, double-blind 3-way crossover design. Performance was assessed using several psychomotor tests: that is, divided attention task, critical tracking task, stop signal task, the attention network test, and the experimental attention switch task. Results demonstrated that evening doses of hydroxyzine impaired performance on the divided attention and the attention network test. Impairment after morning doses was generally larger in magnitude and affected performance measures in all tasks. It is concluded that hydroxyzine-induced impairment at tmax is more prominent after morning doses compared with evening doses and that the present study could not present direct evidence to substantiate the hypothesis that histamine availability inversely affects the magnitude of antihistamine impairment.

Dose-related effects of MDMA on psychomotor function and mood before, during, and after a night of sleep loss

by Silke Conen

Authors:
Wendy M. Bosker, Kim P. C. Kuypers, Silke Conen, and Johannes G. Ramaekers.
Psychopharmacology (Berl). 2010 March; 209(1): 69–76.

Introduction
3,4-methylenedioxymethamphetamine (MDMA) is known to improve psychomotor function and mood when... more Introduction
3,4-methylenedioxymethamphetamine (MDMA) is known to improve psychomotor function and mood when measured during daytime. However, MDMA users tend to take this drug at dance parties while staying awake for prolonged periods of time.
Subjects and methods
This study was designed to assess dose-related residual effects of MDMA on psychomotor function and mood after a night without sleep. Sixteen recreational MDMA users received single doses of 25, 50, and 100 mg MDMA in a randomized, double-blind, placebo-controlled cross-over study.
Results
Results showed that sleep loss significantly impaired psychomotor function. MDMA generally did not affect performance but did improve rapid information processing at the highest dose in the morning after administration. In the evening, MDMA also increased subjective ratings of positive mood at every dose and subjective arousal at the highest dose. These subjective effects were no longer present after a night of sleep loss.
Discussion
It is concluded that sleep deprivation impairs psychomotor function and that stimulant effects of MDMA are not sufficient to compensate for this impairment.

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

by Silke Conen

Authors:
Ramaekers JG, Conen S, de Kam PJ, Braat S, Peeters P, Theunissen EL, Ivgy-May N.
Psychopharmacology (Berl). 2011 May;215(2):321-32.

INTRODUCTION:
Esmirtazapine is evaluated as a novel drug for treatment of insomnia.
PURPOSE:
The... more INTRODUCTION:
Esmirtazapine is evaluated as a novel drug for treatment of insomnia.
PURPOSE:
The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control.
METHODS:
Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine.
RESULTS:
Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected.
CONCLUSION:
It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving.

MDMA (ecstasy) effects on actual driving performance before and after sleep deprivation, as function of dose and concentration in blood and oral fluid

by Silke Conen

Authors:
Bosker WM, Kuypers KP, Conen S, Kauert GF, Toennes SW, Skopp G, Ramaekers JG.
Psychopharmacology (Berl). 2011 Sep 28. [Epub ahead of print]

RATIONALE:
Experimental research has shown that 3,4-methylenedioxymethamphetamine (MDMA) can improve some... more RATIONALE:
Experimental research has shown that 3,4-methylenedioxymethamphetamine (MDMA) can improve some psychomotor driving skills when administered during the day. In real life, however, MDMA is taken during the night, and driving may likely occur early in the morning after a night of "raving" and sleep loss.
OBJECTIVES:
The present study assessed the effects of MDMA on road-tracking and car-following performance in on-the-road driving tests in normal traffic.
METHODS:
Sixteen recreational MDMA users participated in a randomized double-blind placebo-controlled four-way cross-over design. They received single, evening doses of 0, 25, 50, and 100 mg MDMA on separate occasions. Actual driving tests were conducted in the evening when MDMA serum concentrations were maximal and in the morning after a night of sleep loss.
RESULTS:
The primary measure of driving, i.e., standard deviation of lateral position (SDLP, a measure of weaving) was significantly increased during driving tests in the morning in all treatment conditions, irrespective of MDMA dose and concentration. The increments in SDLP were of high clinical relevance and comparable to those observed for alcohol at blood alcohol concentrations >0.8 mg/mL. These impairments were primarily caused by sleep loss.
CONCLUSIONS:
In general, MDMA did not affect driving performance nor did it change the impairing effects of sleep loss. It is concluded that MDMA cannot compensate for the impairing effects of sleep loss and that drivers who are under the influence of MDMA and sleep deprived are unfit to drive.

Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

by Thomas E. Schlaepfer

A 97 Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A, Haazen L, Buntinx E (2011): Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response. Psychological Medicine 41:2089-97.

BACKGROUND:
Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant... more BACKGROUND:
Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.
METHOD:
An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.
RESULTS:
The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression-Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).
CONCLUSIONS:
Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Clozapine: Acquittal of the usual suspect

by Thomas E. Schlaepfer

A 061

This report concerns the case of a 29-year-old male patient suffering from severe psychotic illness who had been... more This report concerns the case of a 29-year-old male patient suffering from severe psychotic illness who had been satisfactorily treated with clozapine for 4 months. Clozapine had also been successfully administered during a psychotic episode 5 years previously. Though symptoms of psychosis were successfully controlled following the most recent psychotic episode, a medical consultation assessed that exacerbation of pancreatitis warranted discontinuation of the current antipsychotic treatment regime. Following a series of unsuccessful courses of neuroleptic medication, a magnetic resonance cholangiopancreaticography (MRCP) revealed marked cholecystolithiasis suggesting a biliary pancreatitis. Clozapine treatment was readministered following cholecystectomy. After 4 weeks of antipsychotic treatment the patient was discharged from hospital on clozapine monotherapy.

The hidden third: improving outcome in treatment-resistant depression

by Thomas E. Schlaepfer

A 106
Schlaepfer TE, Ågren H, Monteleone P, Gasto C, Pitchot W, Rouillon F, Nutt D, Kasper S (2012): The hidden third: improving outcome in treatment-resistant depression. Journal of Psychopharmacology DOI: 10.1177/0269881111431748.

Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to... more Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to evaluate the current status of the field of TRD and reflects the main findings of a consensus meeting held in September 2009. Literature searches were also conducted using PubMed and EMBASE. Abstracts of the retrieved articles were reviewed independently by the authors for inclusion. Evaluation of the clinical evidence in TRD is complicated by the absence of a validated definition, and there is a need to move away from traditional definitions of remission based on severity of symptoms to one that includes normalisation of functioning. One potential way of improving treatment of TRD is through the use of predictive biomarkers and clinical variables. The advent of new treatments may also help by focusing on neurotransmitters other than serotonin. Strategies such as the switching of antidepressants, use of combination therapy with lithium, atypical antipsychotics and other pharmacological agents can improve outcomes, and techniques such as deep brain stimulation and vagus nerve stimulation have shown promising early results. Despite consistent advances in the pharmacotherapy of mood disorders in the last decade, high rates of TRD are still a challenging aspect of overall management.

Lamoure J., Stovel J. A Pharmacists Overview of Alcohol Dependence. Pharmacy Practice 2011; 27(8) CE1-CE10

by Dr. Joel Lamoure

Lamoure J., Stovel J. A Pharmacists Overview of Alcohol Dependence. Pharmacy Practice 2011; 27(8) CE1-CE10

Lamoure J., Stovel J. A Pharmacists Overview of Alcohol Dependence. Pharmacy Practice 2011; 27(8) CE1-CE10 Lamoure J., Stovel J. A Pharmacists Overview of Alcohol Dependence. Pharmacy Practice 2011; 27(8) CE1-CE10

Short-term individual housing induced social deficits in female Mongolian gerbils: Attenuation by chronic but not acute imipramine

by Colin Hendrie

in press
more in press
http://dx.doi.org/10.1016/j.neuropharm.2011.12.016

Mongolian gerbils are highly sensitive to manipulations of their social environments. Housing females individually for short periods (in the order of 7-21 days) has been shown to produce robust and reliable impairments of their subsequent social behaviour. These effects are typified by a marked reduction in the social investigation of an unfamiliar male in a neutral arena and/or a marked increases in levels of freezing whilst and only whilst they are being socially investigated (Immobile in contact). These responses demonstrate housing induced impaired motivation to socially interact.These effects have also been shown to be sensitive to treatment with chronic (but not acute) administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. It was therefore of interest to know if similar effects would be produced by treatment with the tricyclic antidepressant Imipramine. This mixed NA/5-HT reuptake inhibitor first developed in the 1950’s is a commonly used standard in animal models of depression and remains in clinical use today. Female gerbils were individually housed for 7 days or maintained in single-sex groups of 4 for the same period. All animals were then randomly allocated to be administered with either 0, 10 or 20 mg/kg imipramine. Acute administration did not reverse the social impairments produced by the individual housing but did produce non-specific stimulant effects on locomotion in both housing conditions. These social impairments were however reduced after a further 14 days chronic treatment with 10 or 20 mg/kg imipramine and stimulant effects were no longer seen. Following chronic administration in grouphoused animals locomotor stimulation was replaced with sedation, which resulted in a reduction in social behaviour. That is, opposite to the effect seen in Individual housed animals. It is therefore concluded that chronic treatment with imipramine serves to increase social behaviour but only in those animals with a pre-existing social deficit.

Proton magnetic resonance spectroscopy and illness stage in schizophrenia--a systematic review and meta-analysis.

by Stefan Brugger

Aripiprazole in Patients with Bipolar Disorder and Beyond: An Update of Practical Guidance

by Thomas E. Schlaepfer

A 109

BACKGROUND:
Aripiprazole is an atypical antipsychotic with a pharmacological and clinical profile distinct from... more BACKGROUND:
Aripiprazole is an atypical antipsychotic with a pharmacological and clinical profile distinct from other atypical antipsychotics.
SCOPE:
A European multidisciplinary advisory panel of university-based experts in bipolar disorders convened in April 2010 to review new clinical guidelines for the management of mania and the role of aripiprazole in its treatment. This report describes the consensus reached on how best to use aripiprazole in the treatment of mania.
FINDINGS:
Current guidelines recommending aripiprazole for first-line treatment of mania have not generally translated to clinical practice. The panel agreed that clinicians may not feel sufficiently knowledgeable on how to use aripiprazole effectively in mania, and that the perception that aripiprazole is less sedating than other antipschotics may hamper its use. There was consensus about the importance of ensuring that clinicians understood the distinction between antimanic efficacy and sedation. Most acutely manic patients may require night-time sedation, but continuous daytime sedation is not necessarily indicated and may interfere with long-term compliance. If sedation is necessary, guidelines recommend the use of adjunctive benzodiazepines only for a short-time.
CONCLUSIONS:
Clinical practice guidelines widely recommend aripiprazole as a first-line treatment for mania. Although clinical trials may not represent all patient subpopulations, they show that aripiprazole is well tolerated and has a long-term stabilizing potential. The successful use of aripiprazole rests on using the appropriate initial dose, titrating and adjusting the dose as needed and using appropriate concomitant medication to minimize any short-term adverse events. Low incidence of sedation makes aripiprazole a reasonable long-term treatment choice. If short-term sedation is required an adjunctive sedative agent can be added and removed when no longer needed. Clinical considerations should influence treatment choice, and a better distinction between sedation and antimanic effects should be an educational target aimed to overcome potential barriers for using non-sedative antimanic agents such as aripiprazole.

Combining Antidepressants: a Review of Evidence

by Lena Palaniyappan

Lena Palaniyappan, Lisa Insole and Nicol Ferrier

Advances in Psychiatric Treatment

Sequenced (stepped) treatment approaches are widely endorsed in the management of depression. Combining... more Sequenced (stepped) treatment approaches are widely endorsed in the management of depression. Combining antidepressants is a recognised step for those failing to respond to monotherapy. Despite the limited evidence base, this strategy is widely used by clinicians in practice. Not every combination used clinically has a sound neuropharmacological rationale and the use of such combinations may increase the side-effect burden without any additional advantage to the patient. Efficacy of various antidepressant combinations along with the data on side-effect profile and toxicity of such combined treatments are reviewed here. The different combinations are considered by each class of antidepressant available in the UK.