Current Psychopharmacology - Volume 6, Issue 1, 2017

The pharmacological effects on the brain will occur widely in whole brain. Therefore, pharmacological functional MRI (fMRI) is a promising non-invasive tool to investigate the whole brain activation following pharmacological stimulation. The multimodal fMRI techniques, which reflect the vascular response (blood oxygenation level dependent fMRI), neuron/astrocyte activity (diffusion fMRI) and Ca2+ influx in excitatory neurons (manganese enhanced MRI), enable to observe the neuronal activation in rodent model. In the present study, the multimodal pharmacological fMRI method in rodents will be introduced.

Psychiatric polypharmacy is defined as the use of two or more drugs in the treatment of a psychiatric condition. It is widely prevalent in clinical practice. The rationale for polypharmacy is not clear. Etiologic factors are patient demographics (age, gender, race, low socioeconomic status), personality disorder, psychiatric conditions (psychosis, schizophrenia, affective or mood disorders), comorbidities, severity of disease, treatment- refractoriness, prescribing practice, inpatient or outpatient setting, concern for reduction of extra-pyramidal and other sideeffects. Among children and adolescents’ the polypharmacy correlates are age (13 -15 years), male gender, caucasian race, low socio-economic status, medicaid or public insurance, disability, and foster care or child custody outside of biological family. Pediatric polypharmacy is also associated with a diagnosis of behavioral disorder, autism spectrum disorder, ADHD, conduct disorder/ oppositional defiant disorder, personality disorder, violence, tics, psychosis, affective and mood disorder. The concurrent administration of multiple drugs increases the risk of drug interactions and adverse effect including morbidity and mortality. Psychiatric polypharmacy is also associated with cumulative toxicity, poor medication adherence and treatment non-compliance. Thus, psychiatric polypharmacy poses a significant public health problem. However, not all polypharmacy is harmful. Polypharmacy is proven to be beneficial in patients with psychotic, mood or affective disorder, concurrently having dual diagnosis with substance abuse, personality disorder and certain medical conditions including thyroid, pain or seizure disorder. Combination therapy with different class of drugs (antidepressants or antipsychotics) with different mechanism of action have beneficial therapeutic consequences. Therefore, a better understanding of physicians’ rationale for polypharmacy, patient tolerability and effectiveness of prescribing strategy is needed to guide practitioners and to inform the development of evidence based treatment guidelines. Here we review the problem of polypharmacy in psychiatric patients, describe possible etiologic factors, associated consequences and provide recommendations for promoting beneficial polypharmacy and reducing harmful polypharmacy in clinical practice.

Objective: Problem with memory and attention is a neglected aspect of schizophrenia. The most affected domains are attention, working memory and semantic memory. The impairments are, like the negative symptoms, basically stable and independent of the positive symptoms. Since such deficits do not respond to antipsychotics, during the past years some approaches have been done by different acetylcholinesterase inhibitors. Assessment of the effectiveness of rivastigmine, as an add-on therapy, on clinical symptoms of schizophrenia, was the main objective of the present study. Method: 46 male inpatients, with diagnosis of schizophrenia, entered into a 12-week, doubleblind, clinical trial for random assignment to placebo or rivastigmine, as adjuvant to their current antipsychotic medication. ‘Positive And Negative Symptom Scale [PANSS]’ and ‘Mini Mental State Examination [MMSE]’ had been used as the main outcome scales. ‘Clinical Global Impressions- Global Improvement [CGI-I]’ and ‘Extrapyramidal Symptom Rating Scale [ESRS]’ had been used as the ancillary scales. Results: According to the findings, except than significant enhancement of MMSE by rivastigmine [p<0.001], no significant improvement in positive, negative and general psychopathology of schizophrenia was evident in the target and control groups. Also, except than significant enhancement of CGI-I by rivastigmine in intra-group analysis, no significant improvement was apparent in between- group analysis. ESRS, too, did not display any significant alteration in either group. Finally, effect size [ES] analysis exhibited a large improvement of MMSE by means of rivastigmine. Conclusion: Disregard to positive or negative symptoms, rivastigmine can significantly improve the cognitive function of schizophrenic patients, which may be favorable for psychosocial intervention or rehabilitation of this group of patients.

Background: Cocaine is the number one abused psychostimulant drug that reaches addiction criterion in the US. In animals, repeated administration of cocaine results in behavioral sensitization which is thought to represent adaptations in the mesolimbic dopamine neural circuitry, the reward pathway. Cocaine-induced behavioral sensitization is evident in rodents and quail when cocaine is administered intraperitoneally (IP). Objective: The purpose of the current study was to investigate dose-dependent and temporal effects of acute and chronic intramuscular (IM) administration of cocaine in male quail. Method: After habituation to the test chambers, male quail received an IM injection of saline, 3 or 10 mg/kg cocaine and were immediately placed in the chambers. Distance traveled (in meters) was recorded in 5 min time bins for 30 min. Testing was conducted once per day for ten days with each subject receiving the same treatment throughout the experiment. Other behaviors including pecking, preening, and feather fluffing were measured. Results: Cocaine-induced behavioral sensitization and tolerance were evident at relatively low doses of IM cocaine. Dose-dependent effects were evident. IM cocaine also reduced feather fluffing, a behavior that typically occurs during hypothermia. Conclusion: The findings replicated and extended previous research with pigeons and suggested that IM administration of cocaine may be a relatively potent route of administration. Potency of drugs of abuse may be related to the bioavailability of a drug and its addictive properties. Thus, studying drugs of abuse using an IM route of administration may be useful in drug addiction research.

Background: The safety of zopiclone and other Z-drug use has been questioned in many regards. Past issues of side effects, tolerance, abuse, addition, and inappropriate uses have all deserved attention. Objective: In this paper, the issue of zopiclone safety is again reviewed for information newly arising over the last decade. Method: Information databases were scanned for ‘zopiclone’, and all relevant literature was reviewed. Results: Zopiclone continues to be a very frequently consumed sedative-hypnotic. It is often found in the blood of those with drug abuse, self-harm, overdose, and road accidents. The drug is flourishing as a medication for the elderly, and numerous adverse consequences, including injury, have been associated with it. Zopiclone impairs driving ability, and methods to determine such impairment among active drivers are needed. Conclusion: We have previously suggested that zopiclone prescription and use should have the same concerns as those for benzodiazepine pharmacotherapy. There is evidently no need to change such a stance.

Background: Assessments of the residual effects of 3,4-methylenedioxymethamphetamine (MDMA) are typically restricted to experimental studies. The current observational study aimed to investigate the immediate and delayed cognitive, affective and somatic effects of recreational MDMA and other drug use among adults. Method: Thirty-eight adults (26 males and 12 females) aged 19-55 years (mean age 32.1 years) who attended a private recreational event in the Netherlands participated in this study. Demographics and recreational drug use history was recorded at baseline. Participants were categorized a priori into groups based on self-reported drug use at the event and were classified as (1) MDMA and other drug use (N=13, MDMA group), (2) drug use other than MDMA (N=11, DRUGS group), and (3) alcohol only (N=14, ALCOHOL group). Participants completed a daily online survey for one week post drug use, and a past week mood assessment using the Brief Symptom Inventory (BSI) at day7 and day 30 post-drug use. Results: Compared to baseline, the MDMA group reported greater complaints one day post drug use, and some symptoms persisted up to four days. Compared to the MDMA group, the DRUGS group reported greater physical symptoms at one-day post drug ingestion, with some effects present at day 3 post-drug use. No past-week mood differences were detected between groups at day 7 or day 30. Conclusion: Those who consumed MDMA reported greater somatic complaints on day 1, and symptoms of reduced energy, increased fatigue, and weakness persisted up to four days post drug-ingestion.

Objective: In the current research study, a colon targeted pulsatile drug delivery system (PDDS) of venlafaxine hydrochloride (VH) was designed for chronotherapy of depression. Method: A capsular device was designed having body insoluble throughout gastrointestinal tract (GIT) fluid and cap soluble in small intestine fluid. The granules of VH was filled in the body and separated from the cap with the help of a hydrophilic polymer plug. Plugs were made up of blend of HPMC K100M and xanthan gum (1:1). Finally, an enteric coating was applied on entire capsule using 5 %w/v ethylcellulose (EC) solution. Results: In in vitro release studies, the enteric coat of the EC was insoluble for 2 h in pH 1.2 (stomach), but get solubilized in pH 7.4 phosphate buffer (small intestine). The cap of the capsule solubilizes in pH 7.4, which exposed the hydrophilic plug to absorb the nearby fluid and swell. After maximum swelling, the plugs got ejected out from the capsule body causing the release of VH granules into colon (pH 6.8 phosphate buffer). Conclusion: Formulations containing high amount of polymer in plug showed 5 h lag time, which was considered optimum for a delivery system to reach colon and release the drug.

Background: Recent studies show that together with serotonin (5-hydroxytryptamine; 5-HT), leptin also plays an important role in the etiology of depression. Tryptophan increases brain 5-HT but the effects of tryptophan on leptin and responses to stress are not known. Objective: To evaluate the effect of tryptophan load (300mg/kg, orally) on serotonin metabolism, circulating levels of leptin and behavioral responses to single (2hr) and repeated (2hr/day for 6 days) immobilization stress in rats. Method: Albino-wistar rats were randomly assigned to two groups (n = 24) for single and repeated immobilization with further division in four equal groups; water/tryptophan treated unstressed and stressed groups. Behavioral studies and biochemical estimation were performed. Results: Acute exposure to 2hr immobilization decreased food intake, body weight and elicited anxiety like behavior. It increased circulating leptin and brain 5-HT metabolism. The stress-induced behavioral deficits and increases of leptin did not occur following repeated immobilization while the levels of brain 5-HT decreased. Immobilization-induced behavioral deficits were smaller in tryptophan than water treated animals. Tryptophan administration also increased serum leptin levels but inhibited stress-induced increases of leptin. Repeated administration of tryptophan did not increase leptin; tryptophan treated animals exposed to repeated immobilization exhibited smaller leptin levels. Conclusion: Tryptophan induced increases of brain 5-HT reduces stress effects on hormones and behavior but have little effects in unstressed animals suggesting, these increases are available at functional sites only in stressful conditions. While, in control animals these increases occur only intra-neuronally.