Anticholinergic Side Effects Research Articles

Fluvoxamine in obsessive‐compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramine

Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150-300 mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright 2001 John Wiley & Sons, Ltd.

A SHORT-TERM, MULTICENTER, RANDOMIZED DOUBLE-BLIND DOSE TITRATION STUDY OF THE EFFICACY AND ANTICHOLINERGIC SIDE EFFECTS OF TRANSDERMAL COMPARED TO IMMEDIATE RELEASE ORAL OXYBUTYNIN TREATMENT OF PATIENTS WITH URGE URINARY INCONTINENCE

We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.

Pharmacotherapy of depression: a historical analysis.

Iproniazid and imipramine, the prototypes of monoamine oxidase inhibitor (MAOI) and monoamine (re)uptake inhibitor (MAUI) antidepressants, were introduced in 1957. The relationship between iproniazid's antidepressant effect and its MAO inhibiting property was tenuous. Because of the potential drug-drug interactions and the need for dietary restrictions, the use of MAOIs became restricted to atypical depression. The confounding of reserpine reversal with antidepressant effect led to the theory that MAU inhibition is responsible for imipramine's antidepressant effect. Driven by neuropharmacological theory, non-selective reuptake inhibitors were replaced first by selective norepinephrine reuptake inhibitors, then by selective serotonin reuptake inhibitors, and more recently, by a series of new antidepressants to relieve the stimulation of serotonin-5HT2A receptors and the compensatory decline of dopamine in the brain. Each antidepressant has its own identity, but meta-analyses indicate a widening of the antidepressant response range from 65-70% to 45-79%, and a lowering of the antidepressant threshold from 65% to 45%. Although one can no longer expect that 2 of 3 depressed patients will respond to treatment, the newer antidepressants are better tolerated, because they produce less anticholinergic side effects.

Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice

Depression, among other non-cognitive symptoms, is common in patients with dementia. The effect of Hypericum perforatum (St. John's Wort) extract, with well-documented antidepressant activity, was tested on memory retrieval 24 h after training on a one-trial passive avoidance task in mice. Acute administration of Hypericum extract (4.0, 8.0, 12.0, and 25.0 mg/kg i.p.) before retrieval testing increased the step-down latency during the test session. The same doses of Hypericum extract, on the other hand, failed to reverse scopolamine-induced amnesia of a two-trial passive avoidance task. The involvement of serotonergic, adrenergic, and dopaminergic mechanisms in the facilitatory effect of Hypericum extract on retrieval memory was investigated. Pretreatment of the animals with serotonergic 5-HT1A receptor antagonist (−)-pindolol (0.3, 1.0, and 3.0 mg/kg), serotonergic 5-HT2A receptor blocker spiperone (0.01, 0.03, and 0.1 mg/kg), alpha adrenoceptor antagonist phentolamine (1, 5, and 10 mg/kg), beta receptor antagonist propranolol (5, 7.5, and 10 mg/kg), dopaminergic D1 receptor antagonist SCH 23390 (0.01, 0.05, and 0.1 mg/kg), and dopaminergic D2 receptor antagonist sulpiride (5, 7.5, and 10 mg/kg) revealed the involvement of adrenergic and serotonergic 5-HT1A receptors in the facilitatory effect of Hypericum extract on retrieval memory. It is concluded that Hypericum extract may be a better alternative for treatment of depression commonly associated with dementia than other antidepressants known to have anticholinergic side effects causing delirium, sedation and even exacerbating already existing impaired cognition. In dementias of old age, Hypericum perforatum would, therefore, serve as one medication targeting both depression and amnesia with lower potential side effects.

INTRAVESICAL ELECTROMOTIVE ADMINISTRATION OF OXYBUTYNIN IN PATIENTS WITH DETRUSOR HYPERREFLEXIA UNRESPONSIVE TO STANDARD ANTICHOLINERGIC REGIMENS

About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond. A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling. There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations. Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.

Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years ± 9.96 SD were treated with risperidone (RSP) at the dosage of 2–9 mg/die (mean 4.46 mg/die ± 1.30 SD, mean 0.06 mg/kg ± 0.01 SD) for a year. Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.

Effects of nitric oxide donors and nitric oxide synthase substrates on ciliary muscle contracted by carbachol and endothelin for possible use in myopia prevention.

Research has suggested that the development of myopia may possibly be prevented by the use of drugs which facilitate relaxation of the intraocular ciliary muscle. We examined the effects of five nitric oxide-producing agents--two nitric oxide donors, hydralazine and sodium nitrite, and three nitric oxide synthase substrates, L-arginine, L-canavanine, and N-benzoyl-L-arginine ethyl ester--on isolated bovine ciliary muscle maximally contracted with either carbachol or endothelin-1. Of these agents, hydralazine and L-canavanine produced a relaxing effect on endothelin-1-contracted muscle that was significantly greater than relaxing effect on carbachol-contracted muscle. These results indicate that hydralazine and L-canavanine could possibly be used for the prevention of myopia by relaxing the ciliary muscle with few anticholinergic and cycloplegic side effects.

Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia. (UCLA Pain Management Center, Los Angeles, CA) Clin J Pain 2000;16:188–192.

In this double‐blinded, placebo‐controlled study, 49 patients with postherpetic neuralgia (PHN) were randomly assigned to 4 treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with the use of visual analog scales, the McGill Pain Questionnaire, and a side‐effects scale. A statistically significant decrease was seen in pain Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline. Conclude that these data support the effectiveness of amitriptyline in the treatment of PHN, but do not support the addition of fluphenazine.Comment by Lian‐Kah Ti, M.D. Amitriptyline is an established modality of treatment for postherpetic neuralgia. It is believed to exert its effect by its analgesic properties, rather than its antidepressant effect. It has been shown to raise the pain threshold, brought about by its prevention of serotonin re‐uptake.Although isolated case studies suggested a role for fluphenazine in combination with amitriptyline in the treatment of postherpetic neuralgia, the authors could not demonstrate this benefit. This study highlights the difficulties in the treatment of this condition. The use of amitriptyline reduced the intensity of pain, but did not eliminate it (VAS scores decreased from 55.9 to 26.6). When MPQ scores were compared, there was no difference, suggesting that the qualitative aspect of the pain was not reduced. More importantly, the authors noted a ceiling effect for amitriptyline, effectively limiting its potency. Combining therapies may be the answer, but as this study clearly shows, a combination with fluphenazine is not.

Absorption of oxybutynin from vaginal inserts: drug blood levels and the response of the rabbit bladder

Objectives. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. However, one of the major problems with its use is uncomfortable anticholinergic side effects that can lead to discontinuation of treatment. Alternative forms of drug administration may reduce side effects and thus improve patient compliance. Methods. A cylinder-shaped, curved silicone elastomer insert containing oxybutynin was anchored in the vagina of female rabbits. The inserts were designed to release oxybutynin at rates of 0.5, 1.0, and 5.0 mg/day, respectively. Blood drug and metabolite levels were monitored for 1 to 7 days and cystometry was carried out after 7 days of treatment. Results. There was a consistent dose-dependent absorption of the oxybutynin resulting in stable plasma concentrations by 3 days. Levels of N-desethyloxybutynin, the active metabolite that is thought to be responsible for side effects, were less than 1.0 ng/mL in all groups. The cystometrograms showed a decrease in the detrusor pressures for the higher oxybutynin groups and a dose-dependent decrease in micturition pressure. The vaginal wall in contact with the insert showed no irritation. Conclusions. The inserts produced stable blood levels and released sufficient amounts of oxybutynin to have measurable effects on the bladder. There was no irritating effect of the insert on the vaginal wall after a 1-week treatment. Vaginal inserts containing oxybutynin may be an interesting alternative method for the chronic delivery of oxybutynin.

A review of three commonly prescribed skeletal muscle relaxants

Skeletal muscle relaxants (SMR) are commonly used drugs prescribed for the treatment of muscle spasm and discomfort. Although many have been in use for decades, physicians may be unaware of the accumulating evidence of their risks, benefits, safety and side effects. This review examines the efficacy, side effects, and safety of three commonly prescribed SMRs: metaxalone, cyclobenzaprine, and carisoprodol. All three appear to have equal efficacy, but their side effects vary considerably. Metaxalone has the fewest reports of side effects, and no reports of major safety issues. Cyclobenzaprine, closely related to the tricyclic antidepressants, causes the expected lethargy and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances. Carisoprodol raises the greatest concern. Reports in the literature suggest a significant potential for physical and psychological dependence perhaps suggesting a potential for misuse. It also has, perhaps, the greatest toxicity. A secondary goal of this review is to stimulate more discourse about these commonly used, but poorly understood compounds.

Evidence for a Central Cholinergic Deficit in Myasthenia Gravis

Evidence for a Central Cholinergic Deficit in Myasthenia Gravis

Anticholinergic Side Effects Mimic Diseases of Old Age/Anaphylactoid Reactions to Acetaminophen/Olanzapine-Induced Urinary Incontinence/Withdrawal with Quetiapine?/Kidney Stones Associated with Ceftriaxone/Amiodarone-Induced Blue-Gray Syndrome

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), to discuss methods of prevention, and to promote reporting of ADRs to the FDA's medWatch program (1-800-FDA-1088). If you have reported an interesting preventable ADR to medWatch, please consider sharing the account with our readers.

Anticholinergic side-effects of drugs in elderly people.

Anticholinergic side-effects of drugs in elderly people.

Anticholinergic Side Effects in Perspective.

Some of our readers may read the cover and table of contents for this issue of The Primary Care Companion to The Journal of Clinical Psychiatry and sense that they have received a journal of pharmacology by mistake. Further examination of the contents will be reassuring, but I felt it necessary to justify to our readers the presence of a seemingly esoteric study of anticholinergic side effects of 2 atypical antipsychotics—risperidone and olanzapine. This is, after all, a journal dedicated to primary care neuropsychiatric illness. The article by Kennedy et al. is clinical in nature, comparing anticholinergic adverse events experienced by schizophrenic patients taking 2 different medications for which in vitro and in vivo data and experience are at odds. The comparison and the clinical rationale supporting the investigation are sound. Clinicians use perceived side effect profiles as part of the selection process in treatment protocols. Studies of this kind help establish links between bench work studies and clinical trials. Information on expected anticholinergic effects may inform a decision about appropriateness for certain patient groups, such as the elderly. When such investigations might help our readership offer more exacting care to their patients, we are happy to review and publish the results. Another factor in the decision to publish this article on atypical antipsychotics is the topic of atypical antipsychotics themselves. These “novel neuroleptics,” introduced by clozapine in the 1980s, have surpassed older agents except possibly in the use of depot forms of haloperidol or fluphenazine when adherence is problematic. Clozapine is now considered the gold standard neuroleptic where efficacy is concerned. Problems of clozapine-associated agranulocytosis may have limited the use of clozapine to and within the specialty of psychiatry, however. Significantly, the newer atypical antipsychotics risperidone, olanzapine, and quetiapine do not have agranulocytosis as a major concern. Atypical antipsychotics offer several additional advantages over older neuroleptics. They are associated with a lower incidence of the extrapyramidal syndrome—in most patients obviating the need to add additional anticholinergic or dopaminergic medications to treat this side effect common to older agents. They are also associated with a lower risk of tardive dyskinesia—the dreaded and treatment-refractory complication of neuroleptic therapy. Prolactinemia as an adverse effect of dopamine receptor blockade may be reduced by some agents, limiting galactorrhea and irregular menstruation. Finally, and perhaps most significantly, the atypical antipsychotics offer potential efficacy in a broad range of nonschizophrenic illness. Olanzapine is now indicated for the treatment of mania. Other investigations suggest efficacy for atypicals as adjuvants to or augmentations of antidepressants in the treatment of refractory depressed and anxious states, including dysthymia and obsessive-compulsive disorder. Atypical antipsychotics are the next wave of psychotropic medications. Their introduction and appeal parallel those of the SSRIs in the treatment of depressive and anxious states. Just as SSRIs heralded a new opportunity for primary care physicians to treat depression and anxiety more effectively in nonpsychiatric settings, atypical antipsychotics hand those in primary care a new generation of safe and effective agents to offer our patients. Most of us treat, exclusively or collaboratively, some patients with thought disorders or other psychoses, but there is an ever-enlarging therapeutic circle for atypical antipsychotics that already circumscribes a significant portion of our practice. I suggest that we get up to speed on the indications, efficacy, clinical rationale, and differential prescription of these agents as soon as possible. A primer on this very topic will be offered in the Companion very soon.

In Vivo Olanzapine Occupancy of Muscarinic Acetylcholine Receptors in Patients with Schizophrenia

Olanzapine is an atypical antipsychotic with potent antimuscarinic properties in vitro (Ki = 2–25 nM). We studied in vivo muscarinic receptor occupancy by olanzapine at both low dose (5 mg/dy) and high dose (20 mg/dy) in several regions of cortex, striatum, thalamus and pons by analyzing [I-123]IQNB SPECT images of seven schizophrenia patients. Both low-dose and high-dose olanzapine studies revealed significantly lower [I-123]IQNB binding than that of drug-free schizophrenia patients (N = 12) in all regions except striatum. [I-123]IQNB binding was significantly lower at high-dose than low-dose in the same regions. Muscarinic occupancy by olanzapine ranged from 13% to 57% at 5 mg/dy and 26% to 79% at 20 mg/dy with an anatomical pattern indicating M2 subtype selectivity. The [I-123]IQNB data indicate that olanzapine is a potent and subtype-selective muscarinic antagonist in vivo, perhaps explaining its low extrapyramidal side effect profile and low incidence of anticholinergic side effects.

Anticholinergic Differences Among Patients Receiving Standard Clinical Doses of Olanzapine or Clozapine

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

The potential of active metabolites of antihistamines in the management of allergic disease.

Since the discovery of histamine in the ®rst decade of the 20th century, there has been increasing evidence that this biogenic amine, synthesized predominantly in mast cells and basophils, is released in in ammatory processes and plays a key role in the pathogenesis of urticaria and allergic airway diseases, including asthma, rhinitis, and urticaria (1±3). Studies have demonstrated that histamine levels are signi®cantly increased in the bronchoalveolar lavage (BAL) of symptomatic asthmatics, compared with asymptomatic asthmatics (4, 5), and that allergen challenge leads to a marked increase in the levels of histamine in asthmatics (6, 7). Similarly, studies have demonstrated that allergen challenge also leads to signi®cant increases in the levels of histamine in the nasal secretions of patients with allergic rhinitis (8±10). A comparison of patients with chronic urticaria and healthy subjects has also demonstrated that the former release greater amounts of histamine, both spontaneously and after antigen provocation (11±13). In addition, some studies have demonstrated that the responsiveness of the skin to histamine is slightly increased in patients with urticaria (11). Mechanistic studies have demonstrated that the action of histamine arises from its interaction with one of at least three speci®c histamine receptors, H1, H2, and H3, located on various histamine-responsive target tissues. Interaction of histamine with the H1 receptor leads primarily to smooth-muscle contraction, vasodilatation and hypotension, increased vascular permeability with formation of tissue oedema, increased respiratory mucus secretion, and parasympathetic nerve stimulation (14, 15). These effects can subsequently lead to bronchial obstruction in asthma; nasal blockage, sneezing, itching, and discharge in rhinitis; and itchy skin wheals/ ares in urticaria. At the cellular level, histamine may also act on in ammatory cells and lead to release of mediators, such as leukotrienes and cytokines, and increased expression of class II antigens (HLA-DR) and ICAM-1 on epithelial cells (16, 17), effects which could, in turn, exacerbate the pathology and symptoms of allergic disease. In contrast, effects attributable to H2 receptors include augmentation of gastric acid secretion and increases in gastric and respiratory mucus secretion (14). H3 receptors have been implicated in autocrine regulation of histamine synthesis and release from nerve tissue (14).

Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic

Ziprasidone (5-[2-(4-(1,2,-benzisothiazol-3-yl) piperazin-l-yl] ethyl]-6 -chloro indolin-2-one hydrochloride hydrate) is a novel antipsychotic with a pattern of receptor occupancy and preclinical attributes predictive of broad therapeutic efficacy and a favourable tolerability profile in the treatment of psychotic illness. Clinical trials indicate that ziprasidone is effective against positive, negative and affective symptoms in schizophrenia and schizoaffective disorder with minimal motor, cognitive, weight gain, prolactin related, or anticholinergic side effects. In addition, an im. formulation appears to be rapidly effective with significantly less motor side effect liability than haloperidol.

535. Quetiapine for the treatment of psychosis in Lewy body disease

Lewy body disease (LBD) is the second most common cause of dementia in the elderly. Neuropathologic and clinical findings in LBD usually include those of both Parkinson’s disease and Alzheimer’s disease. Psychotic symptoms, in particular visual hallucinations and delusions, are prominent in LBD. The management of psychosis is very difficult, due to the severe neuroleptic sensitivity in this patient population. Quetiapine is a novel antipsychotic medication with 5-HT2 receptor antagonism, and virtually no extrapyramidal and no anticholinergic side effects. This study was intended to assess the efficacy and safety of quetiapine in the treatment of psychosis in LBD. A 52-week trial of open-label, dose-flexible (25–300 mg/day) quetiapine was conducted in patients with LBD, who suffered from psychosis. We enrolled a total of 10 patients (5 females and 5 males) with dementia and parkinsonism, who met the diagnostic criteria for dementia with LBD set by McKeith et al. in 1996. PET perfusion scan of the brain showed bi-temporoparietal hypoactivity in the subjects. All the patients suffered from significant psychosis and required treatment. Psychotic symptoms were measured by the Brief Psychiatric Rating Scale (BPRS). Motor function was measured by the Unified Parkinson’s Disease Rating Scale (UPDRS), the Simpson Scale, and the Abnormal Involuntary Movement Scale (AIMS). The Mini-Mental State Examination (MMSE) evaluated cognitive status. All the scales were applied at Baseline/Week 0, Week 2, Week 4, Week 8, Week 12, week 24, and Endpoint/Week 52. All the patients showed a marked improvement in psychosis as measured by the BPRS, with no significant worsening in motor function or cognitive status. In conclusion, quetiapine is an effective treatment for psychosis associated with LBD. Quetiapine is well tolerated by the LBD patients, despite their extreme sensitivity to extrapyramidal and anticholinergic side effects associated with other antipsychotic agents. Further studies are needed to confirm this pilot data.

Discontinuation of antidepressant drugs during electroconvulsive therapy: a controlled study

Background: The concurrent use of antidepressant drugs with ECT is recommended by a recent ECT guideline. The study aimed to examine differential therapeutic and side effect responses when antidepressants are discontinued or not during ECT. Methods: This study compared the effectiveness and side effect profile of unilateral ECT with antidepressant drugs (Group-1) or unilateral ECT with drug placebo (Group-2) in 30 major depressive disorder (DSM-IV) patients on antidepressants using a prospective randomised trial. Hamilton Rating Scale for Depression (HRSD), Montgomery Asberg Depression Rating Scale (MADRS), UKU scale, Columbia ECT side effect check list were used. The assessments were carried out before starting ECTs and at fixed intervals thereafter for four weeks. In addition, at six weeks a follow-up assessment was carried out using HRSD. ECTs were stopped after four weeks or earlier if patient obtained HRSD scores <8 and remained so for one week. Results: Continuation of antidepressant drugs with ECT conferred no therapeutic advantage. Barring tricyclic antidepressant induced anticholinergic side effects, no differential side effect profile was noted. At follow-up none relapsed in Group-2 and the mean HRSD scores between the groups did not differ. Limitation: The antidepressant treatment prior to ECT was uncontrolled. In addition, the design was not strictly double-blind. Conclusion: The study failed to support an advantage with antidepressant continuation during an ECT course in major depressive disorder.