Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial. Analgesic treatment with levomepromazine in acute myocardial infarction. A randomized clinical trial. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia. Haloperidol as an adjunct analgesic in the management of postoperative pain. Relief of mixed anxiety-depression in terminal cancer patients. Effect of thioridazine. [Tiapride in the treatment of chronic headache (author's transl)]. Tiapride versus glafenine: a double-blind comparative study in the management of acute rheumatic pain. Pimozide therapy for trigeminal neuralgia. Does addition of low-dose flupentixol enhance the analgetic effects of low-dose amitriptyline in somatoform pain disorder?
Drugs influencing monoaminergic pathways are of potential use in the treatment of pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache. Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug. In both treatment groups headache score decreased compared to baseline. Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P = .03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P = .03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted. The efficacy of a non-narcotic analgesic is evaluated in a double-blind randomized series of patients with acute myocardial infarction (AMI). Levomepromazine or pethidine were given in 328 consecutive cases to 316 patients within 24 hours after the onset of symptoms. Levomepromazine, 12.5 mg, appeared as effective as pethidine, 50 mg, in the alleviation of pain, though the initial dose had to be higher. Nausea and vomiting were half as frequent in the levomepromazine group as in the pethidine group (p less than 0.001). The incidences of arrhythmias, lung oedema, hypotension and thromboembolic complications did not differ between the groups. The mortality rate in the first 4 weeks was 22% in the levomepromazine group and 37% in the pethidine group (p less than 0.005), and after one year 39 and 50% (p less than 0.05), respectively. It is concluded that levomepromazine is better tolerated than pethidine in AMI. This suggests that the present management of pain in AMI should be reconsidered. To assess the efficacy and safety of i.v. haloperidol in treatment of acute migraine headache in a double-blind, randomized, placebo-controlled study design.
                Neuroleptics are mainly used as antiemetics in acute migraine. In a previous open trial haloperidol was effective in relieving migraine pain.
                Patients were randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 1 to 3 hours after the infusion and had received placebo, he/she then received haloperidol infusion as an open trial. The open trial also included 7 patients who refused from the placebo-controlled trial. About 1 month after the infusion the patients were contacted by telephone and interviewed about the side effects of the treatment.
                Forty patients were enrolled into the double-blind, placebo-controlled study. Before the infusion the VAS values were 7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain relief was achieved in 80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated with placebo without response together with 7 patients who refused from the placebo-controlled study participated in the open trial. In this group VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. The most common side effects caused by haloperidol were sedation and akathisia, the latter being more troublesome. These effects were very common in patients participating in the double-blind (80%) and open (88%) trials. Sixteen percent of the patients considered the side effects intolerable and would not like the migraine attacks to be treated with haloperidol in the future. Three patients (7%) returned to the emergency ward because of a relapse.
                This study shows that i.v. haloperidol is very effective in relieving migraine-associated pain. Because the majority of the patients had taken other medication without response, haloperidol appears to be an effective rescue medication even when other types of treatment have failed. Relapses are rare, but side effects are common, limiting the use of haloperidol in some patients. Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case.
                In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four 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 use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale.
                A statistically significant decrease was seen in pain in 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.
                These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine. nan nan The therapeutic efficacy of tiapride in chronic headache (300 mg/day orally during 30 days) was studied in a doubleblind trial in a group of 50 patients, 40 of them with so-called "mixed headache", and 10 with classical migraine. The results were subjected to statistical analysis. 65% of treated patients had clinical benefit in the intensity and frequency of headaches. The mode of action of this drug is discussed, together with the involvement of several monoaminergic systems in the genesis of headache. The action of tiapride appears to be indirectly dopaminomimetic as it operates by a blockade of dopaminergic inhibitors receptors. A double-blind study was carried out in 42 patients suffering from acute rheumatic pain to compare the analgesic effectiveness and tolerance of tiapride with that of glafenine, a widely used analgesic in Europe. Patients were allocated at random to receive either 100 mg tiapride or 200 mg glafenine 3-times daily over a period of 14 days. Pain intensity was rated daily by the patients using a visual analogue scale and an overall assessment of response to treatment was made by both patients and physician at the end of the study. The results showed that, whilst both treatments resulted in a marked reduction in mean pain scores, pain disappeared completely in 16 (76%) of the 21 patients treated with tiapride compared with 9 (43%) of the 21 receiving glafenine. There was also a significant difference in favour of tiapride in the physician's overall assessment of response which was considered as excellent in 71% of the patients on tiapride compared with 31% receiving glafenine. Both treatments were well tolerated and few side-effects were reported. Drowsiness occurred in 6 patients on tiapride but this was only mild in 5 and moderate in the other patient. Pimozide was compared with carbamazepine in a double-blind crossover trial in 48 patients with trigeminal neuralgia who were refractory to medical therapy. Pimozide treatment produced greater reduction in trigeminal neuralgia symptoms than carbamazepine treatment. All of the pimozide-treated patients improved, while only 56% of carbamazepine-treated patients were relieved of their pain. Although both drugs provoked some adverse effects, it was not necessary to interrupt the trial in any case. After this 24-week trial, all patients began receiving pimozide and were followed up according to an open-label study design. In all cases, the pimozide dosage was progressively reduced until the minimal effective dose was reached. Central and peripheral mechanisms that may underlie pimozide-induced improvement are discussed. In a double-blind, crossover study, the effects of 75 mg amitriptyline alone during 5 weeks on pain intensity were compared with the effects of a combination of 75 mg amitriptyline and 3 mg flupentixol during 5 weeks in 34 patients with somatoform pain disorder. Both treatments resulted in a statistically significant reduction in pain. However, pain reduction in the combined treatment did not differ from that in the treatment with amitriptyline as a single drug. Neither tardive dyskinesias nor other serious side effects were observed. The results do not support the clinical practice of adding low-dose neuroleptics to low-dose antidepressants in the treatment of somatoform pain disorder.
Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions.
Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies including standardised pain assessment/documentation are warranted.