Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles.

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

An autopsy case of heatstroke under the influence of psychotropic drugs.

We present here a fatal case of heatstroke, involving olanzapine and levomepromazine medications. A male in his sixties was found dead in his storage room in the middle of August, with a high rectal temperature. Autopsy revealed congestion of the lungs without any specific findings. Quantitative toxicological analysis demonstrated concentrations of olanzapine, levomepromazine, 7-aminonitrazepam, and 7-aminoflunitrazepam in a femoral blood sample of 0.433 µg/mL, 0.177 µg/mL, 0.604 µg/mL, and 0.041 µg/mL, respectively. The concentration of olanzapine exceeded toxic levels; however, levomepromazine level was within the therapeutic range. Due to the blocking mechanism of both olanzapine and levomepromazine against muscarinic receptors, they might depress sweating and impair heat dissipation. Based on autopsy findings, results of toxicological examination, and investigation by the authorities, we concluded that the cause of death was heatstroke under the influence of olanzapine and levomepromazine.

Levomepromazine for nausea and vomiting in palliative care.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 4, 2013, on Levomepromazine for nausea and vomiting in palliative care.Nausea and vomiting are common, distressing symptoms for patients receiving palliative care. There are several drugs which can be used to treat these symptoms, known as antiemetics. Levomepromazine is an antipsychotic drug is commonly used as an antiemetic to alleviate nausea and vomiting in palliative care settings. OBJECTIVES: To evaluate the efficacy of, and adverse events associated with, levomepromazine for the treatment of nausea and vomiting in palliative care patients. SEARCH METHODS: For this update we searched electronic databases, including those of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, up to February 2015. We searched clinical trial registers on 7 October 2015 for ongoing trials. SELECTION CRITERIA: Randomised controlled trials of levomepromazine for the treatment of nausea or vomiting, or both, in adults receiving palliative care. We excluded studies in which symptoms were thought to be due to pregnancy or surgery. DATA COLLECTION AND ANALYSIS: We assessed the potential relevance of studies based on titles and abstracts. We obtained copies of any study reports that appeared to meet the inclusion criteria for further assessment. At least two review authors read each paper to determine suitability for inclusion and discussed discrepancies in order to achieve a consensus. MAIN RESULTS: In the original review, we identified 421 abstracts using the search strategy. We considered eight studies for inclusion but ultimately excluded them all from the review. We updated the search in February 2015 and identified 35 abstracts, but again none met the inclusion criteria. We identified two trials from clinical trial registers, one of which is ongoing and one of which was closed due to poor recruitment. AUTHORS' CONCLUSIONS: As in the initial review, we identified no published randomised controlled trials examining the use of levomepromazine for the management of nausea and vomiting in adults receiving palliative care, and our conclusion (that further studies of levomepromazine and other antiemetic agents are needed to provide better evidence for their use in this setting) remains unchanged. We did, however, identify one ongoing study that we hope will contribute to the evidence base for this intervention in future updates of this review.

A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia.

OBJECTIVE: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine, IM haloperidol, and IM levomepromazine in acute agitated patients with schizophrenia. METHODS: The subjects were 122 inpatients. Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation-Calmness Evaluation Scale, and their safety were assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale (BARS), and Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). RESULTS: The mean changes from baseline on the PANSS-EC, Agitation-Calmness Evaluation Scale, Abnormal Involuntary Movement Scale, BARS, and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol. Of these, the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine. The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine. CONCLUSIONS: The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol. No worsening of EPS was observed. Our results also suggest that compared with IM levomepromazine, IM olanzapine is safer and affords greater improvement in symptoms.

Levomepromazine for nausea and vomiting in palliative care.

BACKGROUND: Nausea and vomiting are common, distressing symptoms for patients receiving palliative care. There are several agents which can be used to treat these symptoms. Levomepromazine is an antipsychotic drug which is commonly used to alleviate nausea and vomiting in palliative care settings. OBJECTIVES: To evaluate the efficacy of and adverse events (both minor and serious) associated with the use of levomepromazine for the treatment of nausea and vomiting in palliative care patients. SEARCH METHODS: We searched the electronic databases including CENTRAL, MEDLINE, and EMBASE using relevant search terms and synonyms in March 2013. SELECTION CRITERIA: Randomised controlled trials of levomepromazine for the treatment of nausea or vomiting, or both, for adults receiving palliative care. Studies where symptoms were thought to be due to pregnancy or surgery were excluded. DATA COLLECTION AND ANALYSIS: The potential relevance of studies was assessed based on titles and abstracts. Any study reports which appeared to meet the inclusion criteria were obtained for further assessment. All three authors read these papers to determine their suitability for inclusion and discussed discrepancies to achieve a consensus. MAIN RESULTS: The search strategy identified 421 abstracts from which eight studies were considered but all were excluded from the review. AUTHORS' CONCLUSIONS: No randomised controlled trials were identified examining the use of levomepromazine for nausea and vomiting in palliative care. Further studies of levomepromazine and other antiemetic agents are needed to provide better evidence for their use in this setting.

Methotrimeprazine for the management of end-of-life symptoms in infants and children.

OBJECTIVE: This retrospective chart review assessed the efficacy, dose, and safety of methotrimeprazine in palliating end-of-life symptoms in children and infants. METHODS: A retrospective chart review was conducted of 18 hospitalized pediatric patients who were treated with methotrimeprazine in their last two weeks of life. Data collected included age, diagnosis, symptoms, methotrimeprazine dose, route, efficacy, and any documented adverse effects. RESULTS: Patients' ages ranged from 16 days to 17 years. Underlying conditions included malignancies, trauma, and various neurodegenerative and congenital diseases. All patients (n = 18) were treated for symptoms of agitation, delirium, or restlessness. Most patients also experienced respiratory secretions/congestion (n = 15), pain (n = 13), and/ or dyspnea (n = 9). Less common symptoms included nausea/emesis (n = 5) and spasticity (n = 1). Methotrimeprazine dosages ranged from 0.02 mg/kg/dose to 0.5 mg/kg/dose. Routes of administration included intravenous (n = 13), oral/gastrostomy tube (n = 6), or subcutaneous (n = 4). Sedation (n = 6) was the only documented adverse effect, although when agitation was present, this was potentially an intended and perceived-to-be-beneficial effect. CONCLUSION: Methotrimeprazine, an old drug with diverse receptor activity and multiple routes of administration, appears to be an effective tool in treating complicated end-of-life symptoms in children and infants. This study provides a foundation for analysis with prospective and comparative trials, which may further quantify its benefit.

Prescription persistence and safety of antipsychotic medication: a national registry-based 3-year follow-up.

PURPOSE: Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway. METHODS: Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted. RESULTS: The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine. CONCLUSIONS: Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

Levomepromazine for schizophrenia.

BACKGROUND: Levomepromazine is an 'older' typical antipsychotic medication licensed for use in schizophrenia but sparingly prescribed in the United Kingdom. OBJECTIVES: To determine the clinical effects and safety of levomepromazine compared with placebo or antipsychotic medications for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (December 2008) which is based on regular searches of, amongst others, BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information. SELECTION CRITERIA: All randomised trials comparing levomepromazine with placebo or other antipsychotics for schizophrenia and schizophreniform psychoses were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently. For dichotomous outcomes, we calculated relative risk (RR) (random-effects model), 95% confidence intervals (CI) and, where appropriate, number needed to treat (NNT) was calculated. We avoided the use of number needed to harm (NNH), as an alternative we used number needed to treat for an additional beneficial outcome (NNTB) and number needed to treat for an additional harmful outcome (NNTH) to indicate the direction of effect. For continuous outcomes, we calculated weighted mean differences (WMD). MAIN RESULTS: The review currently includes 4 RCTs with 192 participants. For our primary outcome of leaving the study early, levomepromazine was not significantly different compared with other antipsychotics. The levomepromazine arm was significantly better on CGI severity compared with chlorpromazine (n=38, 1 RCT, WMD -0.80 CI -1.51 to -0.09). Risperidone was better for CGI endpoint scores (n=42, 1 RCT, RR 2.33 CI 1.11 to 4.89, NNT 3 CI 2 to 10) compared with levomepromazine. Recipients given levomepromazine had a better BPRS endpoint score (n=38, 1 RCT, WMD -9.00, CI -17.46 to -0.54) and PANSS total score (n=38, 1 RCT, WMD -15.90, CI -30.30 to -1.50) than chlorpromazine. Risperidone recipients noticed a significant difference for the outcome 'at least 20% reduction' on BPRS endpoint score (n=42, 1 RCT, RR 3.33 CI 1.07 to 10.42, NNT 3 CI 2 to 14) compared with levomepromazine. Levomepromazine caused less tremor (n=41, 1 RCT RR 0.12 CI 0.02 to 0.87 NNTB 3 CI 2 to 8), less antiparkinsonian medication administration (n=79, 2 RCTs, RR 0.39 CI 0.17 to 0.90, NNTB 5, CI 2 to 21) compared with haloperidol. Levomepromazine caused less akathisia compared with chlorpromazine, but more hypotension compared with risperidone (n=42, 1 RCT, RR 2.50 CI 1.21 to 5.18, NNTH 3, CI 2 to 7). Dizziness was common with levomepromazine compared with other antipsychotic medications. AUTHORS' CONCLUSIONS: Available data does not enable us to confidently comment on the effectiveness of levomepromazine for schizophrenia. Larger, more robust, studies comparing levomepromazine with other antipsychotics including clozapine are much needed.

Methotrimeprazine-induced corneal deposits and cataract revealed by urine drug profiling test.

Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test.

Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial.

OBJECTIVES: Methotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy. DESIGN: Double-blind, randomised, controlled trial of methotrimeprazine versus haloperidol. SETTING: 11 palliative care sites in Australia. PARTICIPANTS: Participants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours. INTERVENTIONS: Based on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours. MAIN OUTCOME MEASURES: A ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change. RESULTS: Response to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In the per protocol analysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Complete per protocol response rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm. CONCLUSION: This study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea. TRIAL REGISTRATION NUMBER: ACTRN 12615000177550.

Predictors of remission during acute treatment of first-episode schizophrenia patients involuntarily hospitalized and treated with algorithm-based pharmacotherapy: Secondary analysis of an observational study.

AIM: Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy. METHODS: We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge. RESULTS: Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge. CONCLUSIONS: The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.

[Atypical antipsychotics in elderly patients with dementia]. / Atypiske antipsykotika hos eldre pasienter med demens.

Antipsychotic medication is often prescribed to persons with dementia exhibiting behavioural and psychological symptoms (BPSD). Use of atypical antipsychotics in elderly persons with dementia is associated with an increased risk of serious cerebrovascular adverse events and increased mortality. Based on a review of available literature, we conclude that atypical antipsychotics have a modest effect on BPSD and potentially serious side effects and that conventional antipsychotics appear to have even less favourable effects and adverse event profiles. Antipsychotic medication in patients with dementia exhibiting BPSD should only be prescribed for short-term treatment of severe symptoms associated with considerable distress or serious risk. Non-pharmacological interventions should be the first-line treatment approach in most cases.

Parametric evaluation of methotrimeprazine-midazolam-ketamine and methotrimeprazine-midazolam-ketamine-xylazine combination in dogs.

PURPOSE: To evaluate the parameters of dogs anesthetized by different dissociative drugs protocols through continuous intravenous infusion. METHODS: Thirty healthy dogs of both sexes were assigned randomly to three groups (G1, G2, and G3). G1 was administered with methotrimeprazine as a pre-anesthetic medication, intravenously midazolam-ketamine as bolus for induction and midazolam-ketamine by continuous intravenous infusion for a 60 minute-period of maintenance. G2: the same as for G1. plus an increase in the midazolam dose during maintenance. G3: the same treatment as for G2, plus the addition of xylazine during maintenance. Immediately after induction the anesthetic maintenance started, and measures were taken 15 minutes after pre-medication, at 10 minutes intervals, during maintenance (M0 to M7). RESULTS: Bradycardia, atrioventricular blockage, bradypnea and hypoxemia were shown in G3. G1 and G2 showed a slight hypotension only. CONCLUSION: There were some advantages by using the continuous intravenous via: no parameters oscillation and reduction in the anesthetic recovery period. The increase in midazolam dose brought about little parametric variations which were greater when xylazine was used, with a consequent hypoxemia, bradyarrhytmia, and decrease in respiratory frequency and minute volume.

Sedative use in the last week of life and the implications for end-of-life decision making.

BACKGROUND: The use of sedation at the end of life has aroused ethical controversy, attracting accusations of hastening death by gradually increasing sedative doses. The doctrine of double effect has been introduced as an ethical defense. This study aimed to determine how sedative doses change at the end of life and how often the doctrine of double effect might be relevant. METHODS: Case note review was performed of 237 consecutive patients who died in a specialist palliative care unit. Sedative dose changes during the last week of life were noted and survival from admission was compared between groups of patients receiving no sedation, sedation for 7 days, or a commencement of sedation in the last 48 hours of life. There was detailed review of notes from patients who received a marked increase in sedative dose to explore the applicability of the doctrine of double effect. RESULTS: Sedation was given to 48% of patients. Of these, 13% received sedatives for 7 days or more, while 56% commenced sedative use only in the last 48 hours of life. The groups receiving no sedation or sedation for less than 48 hours had the shortest survival from admission (mean, 14.3 and 14.2 days), whereas the 7-day sedation group survived for a mean of 36.6 days (P<.001). Sedative use and dose increased toward the end of life, but the detailed case note review disclosed only 2 cases where the doctrine of double effect may have been implicated. CONCLUSION: Sedative dose increases in the last hours of life were not associated with shortened survival overall, suggesting that the doctrine of double effect rarely has to be invoked to excuse sedative prescribing in end-stage care.

[Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]. / Traitement des douleurs post-zostériennes par le tramadol. Résultats d'une étude pilote ouverte versus clomipramine avec ou sans lévomépromazine.

To date, no universally applicable recommendations are available for the treatment of patients with postherpetic neuralgia. A mixture of clinical anecdotes, experimental findings and observations from clinical trials form the basis of the medical arsenal for this condition. Tricyclic antidepressants are commonly used, and clinical experience and several investigations have documented their effectiveness. Today, single entity antidepressants, which can be combined with neuroleptics to increase analgesia, are generally recommended for the treatment of postherpetic neuralgia. Some authors also recommend the additional administration of an opioid if analgesia is inadequate. Just over a decade ago, opioids were considered ineffective for the treatment of neuropathic pain; however, more recent investigations relating to the use of opioids, primarily in the treatment of nontumour-related chronic pain, have led to a revision of their use in neuropathic pain. Nevertheless, the use of opioid therapy for neurogenic pain remains controversial. Tramadol is a synthetic, centrally acting analgesic with both opioid and nonopioid analgesic activity. The nonopioid component is related to the inhibition of noradrenaline (norepinephrine) reuptake and stimulation of serotonin (5-hydroxytryptamine; 5-HT) release at the spinal level. In this regard, there are parallels with antidepressants, which are believed to potentiate the effect of biogenic amines in endogenous pain-relieving systems. There is evidence that, in tramadol, both mechanisms act synergistically with respect to analgesia. The aim of this pilot study was to investigate, for the first time, the analgesic efficacy and tolerability of tramadol, compared with the antidepressant clomipramine, in the treatment of postherpetic neuralgia. If necessary, clomipramine was used in combination with the neuroleptic levomepromazine. The study allowed individualised dosages at predetermined intervals up to a maximum daily dose of tramadol 600mg and clomipramine 100mg, or clomipramine 100mg with or without levomepromazine 100mg. 21 (60%) of 35 randomised patients (> or = 65 years) received the study medication over the 6-week period [tramadol n = 10; clomipramine with or without levomepromazine) n = 11]. After 3 weeks' treatment the dosage in both groups remained almost constant for the rest of the 6-week treatment phase (mean daily dose: tramadol 250 to 290mg; clomipramine 59.1 to 63.6mg). Only 3 patients required the combination of clomipramine and levomepromazine. At the outset, both groups recorded an average pain level of 'moderate' to 'very severe'. In correlation with increasing the study medication, this had decreased to 'slight' by the end of the treatment, when 9 of 10 patients in the tramadol group and of 6 of 11 patients in the clomipramine group retrospectively rated their analgesia as excellent, good or satisfactory. The psychological/physical condition of the patients did not change significantly during tramadol treatment. Sensitivity and depression parameters decreased in the clomipramine group. The incidence of adverse events for all patients was similar in both groups (tramadol 76.5%; clomipramine with or without levomepromazine 83.3%). In conclusion, tramadol would appear to be an interesting therapeutic alternative for pain relief in postherpetic neuralgia, particularly in patients who are not depressed. In clinical practice, tramadol and clomipramine can best be used differentially. For example, tramadol could be the drug of first choice in patients with obvious cardiovascular disease (not an uncommon problem in the > or = 65 year age group) in whom antidepressants are contraindicated, and similarly in patients in whom an antidepressant effect is not required. (ABSTRACT TRUNCATED)