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Background: Withdrawal from addictive drugs can be reduced by administering placebo deceptively, but in the clinic it is unethical to deceive the patient. Open-label placebo effects have been observed across a range of psychophysiological phenomena, and may also apply to drug withdrawal. Method: 24-hour abstinent heavy coffee drinkers (N = 61) rated their caffeine withdrawal symptoms before being allocated to one of three groups. The Deceptive group was given decaffeinated coffee (decaf) and told it was caffeinated, the Open-Label group given decaf and told it was decaf and the Control group given water and told it was water. After 45 min, caffeine withdrawal was measured again. All participants rated their expectancies of withdrawal reduction from caffeinated coffee, decaf and water prior to being randomised and the end of the study. Results: There was a significant 9.5-point reduction in caffeine withdrawal in the Open-Label group (95% confidence interval (CI): 4.7, 14.3; p = 0.002), which was 8.6 points less than the Deceptive group (95%CI: 0.4, 16.8; p = 0.014) but 8.9 points greater than the Control group (95%CI: 0.6, 17.2; p = 0.012). Pre-randomisation, participants expected caffeinated coffee to reduce their withdrawal symptoms the most, followed by water and decaf, Pre-randomisation expectancy of withdrawal was only associated with amount of withdrawal reduction in the Deceptive group. Conclusion: It appears as if open-label placebo caffeine (i.e. decaf) can reduce caffeine withdrawal symptoms, even when people do not hold a conscious expectancy it will do so. There may be ways to integrate open-label placebo procedures into clinical interventions for drug dependence without violating informed consent. [ABSTRACT FROM AUTHOR]

Background: Caffeine is the most commonly consumed psychoactive substance, yet its potential reinforcing properties have been understudied. Aims: This study examined the impact of caffeine administration and expectancy on coffee-related craving, withdrawal, and cue reactivity via a balanced-placebo design. Methods: Following 18-h caffeine abstinence, 65 daily coffee consumers (54% male) received either caffeine-containing (100 mg) or placebo gum, along with either accurate or inaccurate information regarding the gum's caffeine content. Participants were exposed to neutral and coffee-related stimuli using different sensory modalities (visual and combined auditory/olfactory). Craving, withdrawal, and heart rate were assessed at baseline and after each cue presentation. Following the cue-reactivity assessments, participants were provided with an opportunity to self-administer units of coffee. Results: Caffeine expectancy was associated with reduced subjective withdrawal 30 min following the gum administration but was not significantly impacted by actual caffeine administration. The presentation of coffee-related cues was found to increase self-reported craving and heart rate, regardless of the expectation that caffeine had been administered. Visual, but not auditory/olfactory, cue reactivity appeared blunted when participants received a prior dose of caffeine. Prior caffeine ingestion also reduced the probability of subsequent coffee self-administration. Conclusion: To our knowledge, this is the first examination of the impact of caffeine administration and expectancy on cue-elicited coffee craving and coffee consumption. Although there was some evidence that caffeine expectancy and administration were found to impact subjective withdrawal and self-administration respectively, neither was found to exert strong consistent effects on cue reactivity. [ABSTRACT FROM AUTHOR]

Background: Animal models are critical to improve our understanding of the neuronal mechanisms underlying nicotine withdrawal. Nicotine dependence in rodents can be established by repeated nicotine injections, chronic nicotine infusion via osmotic minipumps, oral nicotine intake, tobacco smoke exposure, nicotine vapor exposure, and e-cigarette aerosol exposure. The time course of nicotine withdrawal symptoms associated with these methods has not been reviewed in the literature. Aim: The goal of this review is to discuss nicotine withdrawal symptoms associated with the cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure in rats and mice. Furthermore, age and sex differences in nicotine withdrawal symptoms are reviewed. Results: Cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure leads to nicotine withdrawal symptoms such as somatic withdrawal signs, changes in locomotor activity, anxiety- and depressive-like behavior, learning and memory deficits, attention deficits, hyperalgesia, and dysphoria. These withdrawal symptoms are most pronounced within the first week after cessation of nicotine exposure. Anxiety- and depressive-like behavior, and deficits in learning and memory may persist for several months. Adolescent (4–6 weeks old) rats and mice display fewer nicotine withdrawal symptoms than adults (>8 weeks old). In adult rats and mice, females show fewer nicotine withdrawal symptoms than males. The smoking cessation drugs bupropion and varenicline reduce nicotine withdrawal symptoms in rodents. Conclusion: The nicotine withdrawal symptoms that are observed in rodents are similar to those observed in humans. Tobacco smoke and e-cigarette aerosol contain chemicals and added flavors that enhance the reinforcing properties of nicotine. Therefore, more valid animal models of tobacco and e-cigarette use need to be developed by using tobacco smoke and e-cigarette aerosol exposure methods to induce dependence. [ABSTRACT FROM AUTHOR]

Background: The estimated annual prevalence of drug use disorders is as high as 3%, underpinning the need to continually develop more effective treatments. Central nervous system dysregulation, contributing to acute and post-withdrawal syndromes, has traditionally been managed with benzodiazepines; however, a small but growing body of data indicate that the GABAA receptor antagonist, flumazenil, may offer some advantages over traditional management. Aim: To review the literature on the safety and efficacy of flumazenil in benzodiazepine use disorders and identify gaps in the literature. Method: A systematic method was used to identify randomised control trials. Where randomised control trials existed, non-randomised control trials were included to supplement findings. Results: Eleven flumazenil trials were included with varying doses, frequencies and routes of administration. The evidence for flumazenil alone showed generally a reduction in withdrawal symptoms with the exception of one study where withdrawal symptoms initially increased. Flumazenil plus benzodiazepine tapering was assessed in one randomised control trial and a series of non-randomised control trials. Randomised control trial results showed that flumazenil plus benzodiazepine tapering was superior at reducing withdrawal symptoms compared to benzodiazepine tapering alone and placebo. Flumazenil was associated with no serious adverse events; however there remains a risk of seizures. Conclusion: Although flumazenil shows promising efficacy in the management of benzodiazepine use disorders and withdrawal, more randomized control trials are required before a definitive recommendation can be made around its use. [ABSTRACT FROM AUTHOR]

Background: Negative expectancies can exacerbate withdrawal symptoms via the nocebo effect. As such, information provided about dose reductions during attempts to taper a drug could contribute to withdrawal symptoms and increase the likelihood of relapse. The current study tested whether blinding participants to dose reductions during a supervised caffeine dose taper reduced these nocebo-induced withdrawal symptoms.Methods: Three groups of moderate to heavy coffee drinkers had their dose of caffeine reduced (tapered) from 300 mg per day to 0 mg over the course of five days and reported withdrawal symptoms twice daily. Groups were given differing information about how much caffeine they were receiving. An Open Reduction group was given accurate information about dose reductions. A Blind Reduction group was given no dose information whatsoever. A Deceptive Reduction group was misinformed about dose, with instructions suggesting that the dose remained on 300 mg for three days then dropped to 0 mg.Results: The Open Reduction group reported more pronounced caffeine withdrawal symptoms than the Deceptive Reduction group on the days with the greatest discrepancy between actual dose and informed dose, indicating a nocebo effect of open versus deceptive reductions. In addition, the rate of increase in reported withdrawal symptoms in the Blind Reduction and Deceptive Reduction groups was less than that of the Open Reduction group.Conclusion: These results suggest that awareness of dose reductions during a dose taper can result in a nocebo withdrawal effect, and that removing this awareness can reduce withdrawal. This has important implications for standard supervised dose-tapering practice, where patients are aware of the timing and magnitude of dose reductions. [ABSTRACT FROM AUTHOR]

Background: Expectancies have been shown to play a role in the withdrawal syndrome of many drugs of addiction; however, no studies have examined the effects of expectancies across a broad range of caffeine withdrawal symptoms, including craving.Aims: The purpose of the current study was to use caffeine as a model to test the effect of expectancy on withdrawal symptoms, specifically whether the belief that one has ingested caffeine is sufficient to reduce caffeine withdrawal symptoms and cravings in abstinent coffee drinkers.Methods: We had 24-h abstinent regular coffee drinkers complete the Caffeine Withdrawal Symptom Questionnaire (CWSQ) before and after receiving decaffeinated coffee. One-half of the participants were led to believe the coffee was regular caffeinated coffee (the 'Told Caffeine' condition) and one-half were told that it was decaffeinated (the 'Told Decaf' condition).Results: Participants in the Told Caffeine condition reported a significantly greater reduction in the factors of cravings, fatigue, lack of alertness and flu-like feelings of the CWSQ, than those in the Told Decaf condition.Conclusions: Our results indicated that the belief that one has consumed caffeine can affect caffeine withdrawal symptoms, especially cravings, even when no caffeine was consumed. [ABSTRACT FROM AUTHOR]

Background: Distress intolerance is linked to the maintenance of panic disorder and cigarette smoking, and may underlie both problems. Method: Smokers (n = 54; 40.7% panic disorder) were recruited for an experimental study; half were randomly assigned to 12-hour nicotine deprivation and half smoked as usual. The current investigation consisted of secondary, exploratory analyses from this larger experimental study. Four distress intolerance indices were examined as predictors of anxious responding to an emotional elicitation task (10% carbon dioxide (CO2)-enriched air challenge); anxious responding was in turn examined as a predictor of post-challenge panic and nicotine withdrawal symptoms. Results: The Distress Tolerance Scale (DTS) was significantly negatively associated with anxious responding to the challenge (Β = .0.41, p = 0.017). The DTS was negatively associated with post-challenge increases nicotine withdrawal symptoms indirectly through the effect of anxious responding to the challenge (b = .0.485, CI95% (-1.095, -0.033)). This same indirect effect was found for post-challenge severity of panic symptoms (b = .0.515, CI95% (-0.888, -0.208)). The DTS was directly predictive of post-challenge increases nicotine withdrawal symptoms, in the opposite direction (Β = 0.37, p = 0.009), but not panic symptom severity. Conclusions: Anxious responding in response to stressful experiences may explain the impact of perceived distress intolerance on panic and nicotine withdrawal symptom expression. [ABSTRACT FROM PUBLISHER]

When abstinence is an appropriate goal, controlled studies and systematic reviews confirm that rapid, antagonist-precipitated opiate withdrawal procedures are the most effective and cost effective methods of initiating abstinence, and naltrexone (NTX) maintenance. While ‘rapid’ withdrawal, better conceptualised as Rapid Antagonist Induction (RAI), can often be humanely achieved with modest sedation levels, we present three case histories to support our argument that for some patients, general anaesthesia (GA), or techniques of intravenous sedation (IVS) that approach GA, are essential for safety and success. This includes patients with intercurrent disease (e.g. epilepsy or insulin-dependent diabetes) but also those with severe withdrawal phobia after previous distressing experiences. We discuss the history of the procedure. The dangers of RAI under GA or IVS in experienced hands have been exaggerated and the appropriate expertise should be more easily available. Patients and clinicians readily accept risks of major surgery for the excessive intake of food that causes most obesity. Similar risk-acceptance exists in cosmetic surgery and obstetrics. The increasing use and effectiveness of long-acting implants or depot-injections of NTX for relapse-prevention have largely solved compliance problems that undermined the potential of oral NTX. Their ability to prevent opiate overdose in abstinent, non-tolerant patients also strengthens arguments both for offering RAI as a therapeutic option and for reducing psychological, professional and practical barriers to using it. [ABSTRACT FROM PUBLISHER]

Over the last decade there have been further developments in our knowledge of the risks and benefits of benzodiazepines, and of the risks and benefits of alternatives to benzodiazepines. Representatives drawn from the Psychopharmacology Special Interest Group of the Royal College of Psychiatrists and the British Association for Psychopharmacology together examined these developments, and have provided this joint statement with recommendations for clinical practice. The working group was mindful of widespread concerns about benzodiazepines and related anxiolytic and hypnotic drugs. The group believes that whenever benzodiazepines are prescribed, the potential for dependence or other harmful effects must be considered. However, the group also believes that the risks of dependence associated with long-term use should be balanced against the benefits that in many cases follow from the short or intermittent use of benzodiazepines and the risk of the underlying conditions for which treatment is being provided. [ABSTRACT FROM PUBLISHER]

The D2-like dopamine receptors mediate the emotional/aversive state during morphine withdrawal. Given age-dependent differences in the affective responses to withdrawal, this study examined whether the response to dopamine receptor agonists is altered differentially across ages following morphine administration. Adolescent and adult mice were injected with morphine (twice daily, 10–40 mg/kg, s.c.) or saline for 6 days. Subsequently, they were examined for their locomotor response to quinpirole, a D2/D3 receptor agonist, and SKF 38393, a D1 receptor agonist. Quinpirole dose-dependently reduced locomotion in drug-naïve animals. Initial suppression was also observed in morphine-treated animals, but was followed by enhanced locomotion. Notably, this enhanced locomotion was markedly greater in adolescents than adults. Quinpirole-induced hypo-locomotion is thought to be mediated by the presynaptic D2Short receptors, whereas its activating effect is mediated by postsynaptic D2Long/D3 receptors. This suggests that following morphine administration, the postsynaptic, but not the presynaptic, dopaminergic signaling is differentially modulated across ages. This locomotor supersensitivity was not observed for SKF 38393, a D1 dopamine receptor agonist. The D2/D3 receptors are involved in the pathophysiology of many mental illnesses. Thus, this study offers a potential explanation for the increased psychiatric disorder co-morbidities when drug use begins during adolescence. [ABSTRACT FROM AUTHOR]

We have analysed the long-term effects of adolescent (postnatal day 28–43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB1 cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB1 receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB1 and nicotinic receptors. [ABSTRACT FROM PUBLISHER]

We critically appraised all published reports of hypomania and mania following antidepressant termination. To increase reliability and validity we devised diagnostic criteria for an antidepressant discontinuation or withdrawal 'manic state' based primarily on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition substance withdrawal criteria. A systematic literature review identified 24 reports meeting our criteria. Mean age was 39 years (range 18—74), men and women were approximately equally represented, and more cases involved people with unipolar (n = 19) than bipolar disorder (n = 4). The median duration of preceding antidepressant treatment was 12 weeks (range 4 weeks—12 years). All major antidepressant classes were involved (tricyclic antidepressants=13; selective serotonin reuptake inhibitors=5; monoamine oxidase inhibitors=3; selective serotonin-norepinephrine reuptake inhibitors = 2; miscellaneous = 1). More cases followed abrupt antidepressant withdrawal (n = 11) than a tapered withdrawal (n = 6). Six cases appeared to meet the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for a manic episode, with two cases requiring inpatient admission. Of the 24 cases, nine resolved spontaneously without treatment (median duration = 25.5 days), six responded to antimanic drugs, four resolved following antidepressant reinstatement, and treatment was unclear in five cases. We conclude that antidepressant discontinuation hypomania/mania is a valid syndrome. It should be added to the differential diagnosis of hypomania/mania. The clinical implications and possible mechanisms are discussed. [ABSTRACT FROM PUBLISHER]

This study investigated the effect of Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice. Therefore animals were injected with repeated administration of morphine (10 mg/kg, subcutaneous) twice daily for five or six days, in order to make them tolerant or dependent. Rhodiola rosea L. extract (0, 10, 15 and 20 mg/kg) was administered by the intragastric route 60 min prior to each morphine injection (for acquisition) or prior the last injection of morphine or naloxone on test day (for tolerance or dependence expression, respectively). Morphine tolerance was evaluated by testing its analgesic effect in the tail flick test at the 1st and 5th days. Morphine dependence was evaluated by counting the number of withdrawal signs (jumping, rearing, forepaw tremor, teeth chatter) after naloxone injection (5 mg/kg; intraperitoneal) on the test day (day 6). Results showed that Rhodiola rosea L. extract significantly reduced the expression of morphine tolerance, while it was ineffective in modulating its acquisition. Conversely, Rhodiola rosea L. extract significantly and dose-dependently attenuated both development and expression of morphine dependence after chronic or acute administration. These data suggest that Rhodiola rosea L. may have human therapeutic potential for treatment of opioid addiction. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to investigate the effects of a Rhodiola rosea L. extract on the prevention of the development of nicotine dependence and for the reduction of abstinence suffering following nicotine cessation in mice. Dependence was induced in mice by subcutaneous injections of nicotine (2 mg/kg, 4 times/day) for eight days. Spontaneous abstinence syndrome was evaluated 20 h after the last nicotine administration, by analysis of withdrawal signs, as affective (anxiety-like behaviour) and physical (somatic signs and locomotor activity). Rhodiola rosea L. extract was administered orally during nicotine treatment (10, 15 and 20 mg/kg) or during nicotine withdrawal (20 mg/kg). Results show that both affective and somatic signs (head shaking, paw tremors, body tremors, ptosis, jumping, piloerection and chewing) induced by nicotine withdrawal are abolished by administration of Rhodiola rosea L. extract in a dose-dependent fashion, during both nicotine exposure and nicotine cessation. In conclusion, our data encourage additional studies to define the use of R. rosea L. as a therapeutic approach in the treatment of smoking cessation. [ABSTRACT FROM PUBLISHER]

Nicotine dependence has been linked to attention-deficit hyperactivity disorder (ADHD) symptoms in both clinical and general populations. This behavioural pharmacology study used a within-subject, double-blind, crossover design to test the effects of atomoxetine, a medication for ADHD, on nicotine abstinence symptoms. Fifty non treatment-seeking smokers (=15 cigarettes/day) completed a baseline session when they were smoking as usual and then two laboratory testing sessions after overnight abstinence and treatment with 7 days of either atomoxetine (1.2 mg/kg) or placebo. During each laboratory session, participants completed subjective measures of abstinence symptoms and performed neurocognitive tasks. In mixed effects models, atomoxetine, compared with placebo, was found to be associated with a reduction in abstinence-induced subjective withdrawal symptoms. Atomoxetine was also associated with significant reductions in self-reported smoking urges amongst smokers who scored high on a baseline measure of smoking for stimulation. However, atomoxetine had no effect on any of the cognitive tasks employed in the study. Thus, atomoxetine may reduce cravings to smoke among smokers who use nicotine to increase arousal. [ABSTRACT FROM AUTHOR]

Cannabis is the most widely used illicit substance in the world. Estimates suggest that approximately 10-20% of cannabis users meet criteria for cannabis dependence and a significant proportion experience withdrawal discomfort on cessation of use. To date, there has been an absence of any clinically validated treatments to manage withdrawal. The current study is an open-label trial exploring the utility of lithium carbonate for the management of cannabis withdrawal symptoms in treatment seeking adult humans. In total, 20 participants were recruited to the study (19 men). All met DSM-IV cannabis-dependence criteria and had been smoking cannabis daily or almost daily for a mean 9 years. Participants were admitted to an inpatient detoxification facility and prescribed lithium 500 mg b.d. for 7 days. Cannabis withdrawal was assessed daily with the Marijuana Withdrawal Checklist (MWC). Two participants were withdrawn from the trial because of possible adverse effects. Sixty percent of participants completed the 7-day treatment program. Follow-up was conducted at a mean of 107 days following treatment. The mean percentage of days abstinent in the period between treatment cessation and follow-up was 87.57%. Twenty-nine percent of participants (n = 5) reported continuous abstinence that was biochemically verified at follow-up. Agreement between self-reported cannabis use and urinalysis at follow-up was moderate (ê = 0.47). Significant reductions in symptoms of depression and anxiety and cannabis-related problems were also reported. This study provides evidence for the potential clinical utility and safety of lithium in the management of cannabis withdrawal. A randomised, placebocontrolled trial is recommended. [ABSTRACT FROM AUTHOR]

Craving for caffeine has received little empirical attention, despite considerable research into the potential for caffeine dependence. The main aim of this study was to develop, and initially validate, a multi-item, multidimensional instrument to measure cravings for caffeine. Participants were 189 caffeine consumers who completed the Questionnaire of Caffeine Cravings, which was based on the Questionnaire of Smoking Urges (QSU), in one of five naturally occurring periods of abstinence; 1-15min; 16-120mins; 3-7h; 12-48 h and +48h. Exploratory factor analysis suggested a three-factor solution best described the data; Factor 1 reflected strong desires, intentions and positive reinforcement; Factor 2 reflected mild/general positive and negative reinforcement and Factor 3 reflected functional/mood-based negative reinforcement. Significantly higher Factor 1 and Factor 2 scores were recorded for high frequency users; significantly higher Factor 1 and Factor 3 scores were recorded as a function of increased levels of dependence. Duration of abstinence did not significantly effect cravings across all three factors. Regression analyses suggested level of dependence best predicted both current cravings and frequency of daily use. These findings suggest caffeine cravings may be conceptualized multidimensionally and further validates the use of multidimensional, multi-item instruments. Cravings for caffeine may manifest and be detected across varying levels of dependence and, frequency of use and independently of duration of abstinence. [ABSTRACT FROM AUTHOR]

Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chtordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels. [ABSTRACT FROM AUTHOR]

Children who have taken psychostimulants long term for attention deficit/hyperactivity disorder (ADHD) are now presenting at adult psychiatry clinics at an age at which bipolar disorder and schizophrenia may first appear and at which pregnancy is a possibility. Doctors who may have little experience in the management of ADHD or use of psychostimulants are faced with decisions on whether to continue or withdraw medication. A literature search conducted to clarify these issues revealed that, although psychostimulants are generally efficacious in ADHD, the risks of withdrawal reactions and of possible long-term effects such as drug addiction, psychosis and depression, or effects in pregnancy, have not been adequately investigated. In particular, there is little information on the effects of withdrawal and no firm guidelines on methods of psychostimulant discontinuation. There is a need for further research to clarify the pharmacological issues involved in the drug treatment of ADHD and for overlapping arrangements between child and adult psychiatry clinics in the management of ADHD. [ABSTRACT FROM AUTHOR]

Atypical antipsychotics offer broader efficacy and improved tolerability compared with conventional agents. Many patients currently treated with conventional antipsychotics continue to experience persistent symptoms or troublesome side effects and may benefit from a change to one of the newer atypical agents. There are also significant differences in the side-effect profiles of the atypicals, such that a switch from one atypical agent to another could offer advantages to many patients. Unfortunately, many clinicians remain uncertain about the switching process and are reluctant to initiate change. The aim of this review is to identify the indications for a switch in antipsychotic therapy with a focus on recent switching data for the atypical antipsychotic, quetiapine. The clinical aspects of quetiapine's receptor binding characteristics are reviewed including the implications of the low D2 antagonist properties that make quetiapine the treatment of choice when EPS persists with other atypical antipsychotics. Practical guidelines are given for managing the process of changeover, for avoiding pitfalls and for maximizing the chances of a successful switch. For example, when managing the antipsychotic crossover, it is important to consider the psychological effects of switching arising from symptom and side-effect changes. Finally, advice is provided on the assessments necessary when evaluating the success of a change in therapy, together with guidance on the optimal duration of treatment trials. [ABSTRACT FROM AUTHOR]

This study aimed to examine the behavioural and neurochemical (cannabinoid CB1 receptor gene expression) changes induced by spontaneous cannabinoid withdrawal in mite. Tolerance was assessed by measuring rectal temperature and motor activity in the open-field test after CP-55, 940 administration. Cannabinoid withdrawal symptoms were determined by measuring motor activity and behavioural signs of abstinence. Cessation of CP-55, 940 treatment in tolerant mice induced a spontaneous time-dependent behavioural withdrawal syndrome consisting of marked increases (140%} in motor activty, number of rearings (170%), decreases in grooming (57%), wet dog shakes (73%} and rubbing behaviours (74%) on day 1, progressively reaching values similar to vehicle-treated mice on day 3. Interestingly, this spontaneous cannabinoid withdrawal resulted in CB1 gene expression upregulation (20-30%} in caudate-putamen, ventromedial hypothalamic nucleus, central amygdaloid nucleus and CA1, whereas in the CA3 field of hippocampus, a significant decrease (15-20%) was detected. Taken together, the results of this study suggest that cessation of CP-55, 940 administration in tolerant mice produces a behavioural cannabinoid withdrawal syndrome and a selective and differential responsiveness in CB&1 receptor gene expression in several brain regions of the mice. These findings further suggest a time and regional differential role for cannabinoid receptors in short- and Long-term neuroadaptations that occur after exposure to cannabis derivatives. [ABSTRACT FROM AUTHOR]

Recent years have seen a considerable media interest in the adverse effects of the selective serotonin reuptake inhibitors (SSRIs). This has led to claims that these antidepressants may lead to suicide and homicide and that they cause dependence or even addiction. Such claims have caused great concerns to many patients and have confused doctors in both primary care and psychiatric practice. In this article I review the basis of these claims and show that many seem to emerge from the misinterpretation of evidence and the use of imprecise definitions. Although the SSRIs are not free of problems they compare very favourably with other antidepressants and other classes of psychotropic drugs. There is no evidence they are addictive in the formal sense of leading to a drug dependence syndrome. Some suggestions on the way these issues can be more precisely defined and studied in future are given. [ABSTRACT FROM AUTHOR]