Amitriptyline with perphenazine

Gas Chromatographic Determination of Amitriptyline, Nortriptyline and Perphenazine in Plasma of Schizophrenic Patients After Administration of the Combination of Amitriptyline with Perphenazine Arzneim.-Forsch. 29(1) 158-161 (1979) CA 90 145440m... 

One of the more methodologically rigorous studies on the utility of TCA/antipsychotic combinations in treating PMD was completed by Spiker et al. [1985). In this study, 54 patients who met criteria for depression with psychotic features on the Schedule for Affective Disorders and Schizophrenia [Endicott and Spitzer 1978) and by Research Diagnostic Criteria [Spitzer et al. 1985) were randomly selected to treatment with amitriptyline alone, perphenazine alone, or the combination of two drugs. After a 7-day placebo washout, patients were treated for 35 days with doses averaging approximately 50 mg/day of perphenazine and approximately 200 mg/day of ami-... 

A collaborative VA study (364) found that the addition of imipramine or a monoamine oxidase inhibitor to CPZ did not benefit chronic psychotic patients any more than CPZ alone. Further, the addition of an amphetamine was slightly harmful. This finding has since been replicated in several studies on apathetic schizophrenic patients (365). A study of chronic ambulatory schizophrenics compared amitriptyline plus perphenazine with perphenazine alone ( 366). While they found the combination slightly better in ameliorating depressive symptoms, it was at the cost of a slight increase in patients thought disorder. 

Anton RF, Burch EA. Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression. Am J Psychiatry 1990 147 1203-1208. 

A 50-year-old woman with an electroencephalographic abnormality but no history of epilepsy, who had taken amitriptyline and perphenazine uneventfully for years, suffered two seizures 18 days after switching to trazodone 50 mg/day. 

Berger and Wilson also reported the separation of 10 antidepressants (amitriptyline, imipramine, nortriptyline, desipramine, protripyline, bucliz-ine, benactyzine, hydroxyzine, perphenazine, and thioridazine) using a packed-column SFC with a tertiary mobile phase [37], A Lichrosphere cyanopropyl column with a mobile phase consisting of supercritical fluid carbon dioxide with 10% modifier (methanol with 0.5% isopropylamine) was used for the separation. It was noted that solutes did not elute without the addition of isopropylamine. Detection limits obtained were as low as 88 ppb for a 5-jul injection. 

A 68-year-old man, who had been taking lorazepam, perphenazine, and amitriptyline for many years, developed acute thrombocytopenic purpura after combination therapy of chlordiazepoxide 5 mg and clidinium 2.5 mg tds for irritable bowel syndrome (2). His disease improved after withdrawal of chlordiazepoxide and clidinium and treatment with intravenous prednisolone. 

Clinically important, potentially hazardous interactions with amiodarone, amisulpride, amitriptyline, amoxapine, arsenic, bepridil, bretylium, calcium, chlorpromazine, clomipramine, desipramine, disopyramide, doxepin, erythromycin, fluphenazine, imipramine, iron salts, magnesium, mesoridazine, nortriptyline, pentamidine, perphenazine, phenothiazines, pimozide, procainamide, prochlorperazine, promazine, promethazine, protriptyline, quinidine, sotalol, sucralfate, thioridazine, tricyclic antidepressants, trifluoperazine, trimipramine, zinc salts... 

Perphenazine/amitriptyline are indicated in the treatment of moderate to severe anxiety or agitation and depressed mood moderate to severe depression and anxiety associated with chronic physical disease treatment of patients in whom depression and anxiety cannot be clearly differentiated and treatment of schizophrenia with associated depression. 

Most APDs, as well as TCAs, are inhibitors of the cytochrome P450 enzymes, thus potentially increasing each other s serum levels. For haioperidoi, an increase in serum levels of TCAs (by about 2-fold) is found in up to 10% of patients treated with ciomipramine or nortriptyiine (but is not found with desipramine). Levomepromazine can significantly increase ciomipramine serum levels. Perphenazine has been found to increase serum levels of amitriptyline, desipramine, and nortriptyiine, while thioridazine has been reported to increase desipramine serum levels. Thiothixene levels are usually increased by TCAs such as doxepin, nortriptyline, and clomipramine (the latter combination increases the risk for tardive dyskinesia). 

Most antipsychotic drugs as well as tricyclic antidepressants (TCAs) are inhibitors of the chytochrome P450 liver catabolic enzymes, thus potentially increasing each other s serum levels. Chlorpromazine increases imipramine serum levels. Levomepromazine can cause a significant increase in clomipramine serum levels. Perphenazine has been reported to increase the serum levels of amitriptyline, desipramine, imipramine, and nortriptyline. Thioridazine has also been shown to increase TCA serum levels (mainly desipramine). Marked extrapyramidal side-effects have been reported in a few cases with fluphenazine or perphenazine when fluoxetine was added to the regimen. The mechanism is not known. A mutual increase in serum levels of both thioridazine and paroxetine is evident when these agents are... 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

Vitamin C 1 g three times daily was found to have no effect on the urinary excretion of methotrexate 45 mg given intravenously to a woman with breast cancer, despite the urine becoming more acidic at pH 5.9 (compare Methotrexate + Urinary alkalinisers , p.654). She was also receiving oral cyclophosphamide, propranolol, amitriptyline, perphenazine and prochlorperazine. No special precautions appear to be necessary. 

The simultaneous dissolution profile of two compounds with overlapped spectra has been solved using different mathematical approaches. Derivative spectrophotometry is a solution used for the couples sulfadiazine-trimethoprim, amitriptyline-perphenazine, sulphamethoxazole-trimethoprim, amoxicilline-bromhexine, and amoxicillin-clavulanic acid. This strategy has been used to obtain three dissolution profiles, namely, the standard (global) profile and two individual profiles such as sulphamethoxazole-trimethoprim or hydrochlorothiazide-captopril. 

A controlled trial in unselected depressed patients showed that the combination of amitriptyline (25 mg) and perphenazine (2 mg) was more effective than imipramine (25 mg).28 a doubleblind study in acutely depressed patients, comparing a combination of amitriptyline (25 mg) and fluphenazine (0.5 mg) with amitriptyline (25 mg), showed that the combination was better in relieving the symptoms associated with depression.29 Lithium carbonate was found to be highly effective in the treatment of mania but was less effective in the treatment of depression.20 The lithium salts and the tricyclic antidepres-... 

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