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PubMed1983

The effects of protriptyline in sleep-disordered breathing.

The effects of therapy with the tricyclic antidepressant protriptyline were studied in 12 patients with hypersomnolence and moderately severe sleep apnea. After treatment there was no significant change in the duration or frequency of sleep-disordered breathing (SDB) during non-REM sleep, but there was an alteration in the breathing pattern characterized by a decrease in the amount of apnea during SDB events. Apnea, as a percent of disordered breathing time, fell from 60.4 +/- 27.2% to 35.5 +/- 26.7% (p less than 0.01) and was accompanied by a reduction in the peak fall in oxygen saturation from 16.2 +/- 6.2% to 9.2 +/- 4.7% (p less than 0.01). During REM sleep there was no change in the pattern, duration, or frequency of SDB, or reduction in the peak fall in oxygen saturation. However, there was a reduction in the amount of Stage REM sleep, thereby reducing the more severe SDB events (p less than 0.01) and further improving nocturnal oxygenation. In 10 of 12 patients, there was subjective improvement in daytime hypersomnolence, which was associated with an increase in median sleep onset time from 3.3 +/- 2.2 to 5.1 +/- 2.1 min (p less than 0.01). Although all patients developed mild side effects from the anticholinergic properties of protriptyline manifested by a dry mouth, 4 patients noted additional side effects including urinary hesitancy, mild constipation, and difficulty in maintaining an erection. One patient developed intolerable constipation that necessitated discontinuation of the drug. We conclude that protriptyline reduced daytime hypersomnolence and altered the pattern of SDB, thus improving gas exchange and oxygenation during sleep. Therefore, in selected patients with moderately severe obstructive sleep apnea, therapy with protriptyline is an alternative to surgical treatment with a tracheostomy.

Adult↗
PubMed1985

Differential elevation by protriptyline and depression by diazepam of upper airway respiratory motor activity.

Effects of systemically administered protriptyline and diazepam on the respiratory activity of the phrenic, hypoglossal, and recurrent laryngeal nerves were investigated in vagotomized, decerebrate cats. Both hypoglossal and recurrent laryngeal nerve activities were consistently increased after protriptyline administration, whereas the phrenic nerve discharge was not systematically altered. Similar changes were observed in cats with bilateral carotid sinus nerve sections. Diazepam induced a reduction of hypoglossal and recurrent laryngeal nerve activities at doses that did not alter phrenic nerve discharge. These results with diazepam were the same in carotid chemodenervated cats. We conclude that neural mechanisms controlling upper airway muscles are much more sensitive to protriptyline and diazepam than are those of the bulbospinal-phrenic system. The selective augmentation of hypoglossal and recurrent laryngeal discharges by protriptyline could account for the reported decrease in the frequency of obstructive sleep apneas in patients receiving this antidepressant. In contrast, diazepam, by depressing motor activity to upper airway muscles, may exacerbate oropharyngeal obstruction during sleep.

Animals↗
PubMed1977

Protriptyline plasma levels and antidepressant response.

Twenty-one depressed outpatients were treated for 4 wk with 20 mg/day of protriptyline. Protriptyline plasma in individuals after 4 wk ranged from 22 ng/ml to 167 ng/ml. There was a negative correlation (-0.50, less than 0.05) between the severity of depression measured by the Hamilton Rating Scale (HRS) and the wk 4 protriptyline concentration. Patients with plasma levels above 70 ng/ml (wk 4) had better outcomes measured by the HRS (p less than 0.05) and the Zung Self-Rating Depression Scale (p less than 0.05) and had greater percent decreases on both scales (p less than 0.05) during treatment than those with lower plasma levels. An upper limit to the therapeutic plasma level range beyond which response to treatment was less satisfactory was not demonstrated in this study.

Adult↗
PubMedDate not supplied

Protriptyline, chronic tension-type headaches, and weight loss in women.

Twenty-five women with chronic tension-type headaches were treated with protriptyline for 3 months, with attention paid to days of monthly headaches before and while taking the medication, as well as change in weight and side effects. One patient stopped the medication because of side effects and 2 did not return for follow-up, yielding 22 patients. The typical dose of protriptyline was 20 mg every morning. Eighty-six percent of patients had fewer headaches each month, with the mean dropping from 28.2 to 11.7 days. Seventy-three percent had a 50% or greater reduction in the number of headaches per month. The average weight change was a loss of slightly over 3 pounds during the study period. The advantages and disadvantages of protriptyline in the treatment of chronic tension-type headaches are discussed, as are mechanisms of action.

Adolescent↗
PubMed1982

Protriptyline in obstructive sleep apnea: a double-blind trial.

We evaluated protriptyline, a nonsedating tricyclic antidepressant, as a treatment for obstructive sleep apnea in a double-blind crossover study of five men. After two weeks of treatment, with no change in body weight, daytime somnolence was markedly reduced and nocturnal oxygenation was improved, although apnea duration and frequency were not significantly decreased. Rapid-eye-movement (REM) stage time as a fraction of the total sleep time was reduced during treatment from 0.231 +/- 0.031 to 0.107 +/- 0.013 (mean +/- S.E.M.) (P less than 0.05). REM apnea time as a fraction of total sleep time was reduced from 0.145 +/- 0.022 to 0.054 +/- 0.006 (P less than 0.05). REM reduction during treatment with protriptyline can account for decreased REM apnea time. Similar decreases in REM stage time and REM apnea duration and similar improvement in oxygenation continued after six months of treatment. In addition, body weight, apnea, and arousal frequency were decreased at this time. Although the obstructive sleep apnea was not resolved, it was reduced. Protriptyline can be effective in patients with sleep apnea when the disorder is not life-threatening.

Adult↗
PubMed1988

Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome.

The role of drug therapy in the treatment of the sleep apnea/hypopnea syndrome is unclear. In a randomised, double-blind, placebo-controlled study, we investigated the value of 14-day therapy with protriptyline (20 mg daily) or acetazolamide (250 mg 4 times per day) on symptoms and on the frequency of apneas, hypopneas, arousals, and 4% desaturations in 10 patients with obstructive sleep apnea/hypopnea syndrome. Overall, protriptyline did not have a significant effect either on symptoms or on any of the above polysomnographic criteria. Acetazolamide reduced the apnea/hypopnea frequency [placebo 50 +/- 26 (SD); acetazolamide 26 +/- 20/h of sleep, p less than 0.03] and tended to decrease the frequency of 4% desaturations (placebo 29 +/- 20; acetazolamide 19 +/- 16/h of sleep, p = 0.06). Despite these physiological improvements, acetazolamide did not significantly improve symptoms and paraesthesiae were common. Contrary to earlier studies, we conclude that protriptyline may have a limited role in the treatment of the sleep apnea syndrome. The reason why acetazolamide produced a physiological, but not a symptomatic, response requires further investigation.

Acetazolamide↗
PubMedDate not supplied

Protriptyline as an alternative stimulant medication in patients with brain injury: a series of case reports.

The results of a series of eight individual case reports in which protriptyline, an activating tricyclic antidepressant, was used as a 'stimulant' medication are presented. For some patients with head injury, traditional stimulants, such as methylphenidate, or dopaminergic stimulants, such as levodopa-carbidopa, amantadine, or bromocriptine, may be partially or totally ineffective or not tolerated. Protriptyline can be a very effective alternative and, for some patients, may be the most effective stimulant tried. In low to moderate doses, protriptyline should be considered for trials as an activating/stimulant medication in patients with head injury.

Activities of Daily Living↗
PubMed1990

The use of protriptyline for respiratory failure in patients with chronic airflow limitation.

Treatment of nocturnal hypoventilation in patients with restrictive chest wall disease and respiratory failure, results in improved daytime arterial blood gas tensions, increase in functional ability and longer survival. Success has been achieved with the use of protriptyline which reduces the duration of rapid eye movement (REM) sleep during which nocturnal hypoventilation occurs. Eighteen patients with severe chronic airflow limitation (CAL), took part in a randomized, double-blind, crossover trial of protriptyline and placebo. Seventeen patients completed the study. The use of protriptyline was associated with a fall in the median percentage of total sleep time spent in REM from 16 to 8.8% (p less than 0.01). This was associated with a reduction in the median daytime arterial carbon dioxide tension from 6.4 kPa (range 5.2-8.5 kPa) to 5.8 kPa (range 5.0-8.1 kPa) (p less than 0.01); increased respiratory muscle strength (p less than 0.05), and increased six minute walking distance from a median of 258 m (range 58.5-585 m) to 275 m (range 171-598 m) (p less than 0.02). We found pharmacological treatment of REM-related nocturnal hypoventilation in patients with CAL to be effective, but anticholinergic side-effects, particularly in older male patients, might preclude long-term treatment.

Adult↗
PubMed1989

Effect of protriptyline on ventilatory responses to hypercapnia and asphyxia in normal subjects.

A double-blind crossover study was undertaken to assess the effect of protriptyline on ventilatory responses in normal subjects. Seven subjects received in random order placebo, 10 mg and 20 mg protriptyline daily for 2 weeks. Measurements of hypercapnic ventilatory response (HCVR) and asphyxial hypoxic ventilatory response (HVR) were made before treatment, 6-8 h after the first dose, and after 2 weeks treatment. Mean HCVR and HVR following 10 mg and 20 mg protriptyline did not differ significantly from measurements on placebo, neither for the single dose study or after 2 weeks.

Adult↗
PubMedDate not supplied

The role of protriptyline in obstructive sleep apnea.

Protriptyline, a non-sedating tricyclic agent, was evaluated in a double blind drug-placebo crossover trial in five obese patients with obstructive sleep apnea. Four of the five patients had improvement in somnolence. Protriptyline improved oxygenation. This seemed related primarily to a reduction (from 23% to 11%) in REM, with fewer of the more severe REM apneas. Arousal frequency remained quite high; thus the reason for the reduction in somnolence remains unclear. In three patients, at six months the improvement in clinical status and oxygenation persisted. We have now attempted long term treatment in nine patients. In five, anticholinergic side-effects necessitated stopping therapy. Four patients continue to do well. A trial of protriptyline is thus indicated in treatment of mild to moderate obstructive apnea or when the patient refuses more invasive treatment.

Adult↗
PubMed1986

[Fatal poisoning by protriptyline and haloperidol following an extreme overdose].

In this paper the authors report on a case of lethal suicidal toxification with protriptyline and haloperidol after oral ingestion. Gas chromatographic and radioimmunologic investigations were used for quantitative determination of protriptyline and haloperidol in blood, urine, and tissues. The highest concentrations were found in lung and liver. These concentrations are discussed with reference to the cause of death.

Adult↗
PubMed1975

The effects of protriptyline and clomipramine in vitro on the uptake of 5-hydroxytryptamine and dopamine in human platelet-rich plasma.

The effects of protriptyline and clomipramine, at concentrations of 10(-7)M to 10(-4)M, were studied in vitro on the uptake of 5-hydroxytryptamine and dopamine uptake in human platelet-rich plasma. It was found that the tertiary amine, clomipramine, was a more potent inhibitor of 5-hydroxytryptamine uptake than the secondary amine, protriptyline. The activity of both compounds was competitive but it was thought unlikely that they acted through tryptamine receptor sites as methysergide 2.5 X 10(-8)M had very little effect on 5-hydroxytryptamine uptake. Neither tricyclic antidepressant had any marked effect on dopamine uptake.

Binding, Competitive↗
PubMed1979

Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation.

A 51 year old woman sustained ventricular fibrillation while receiving perphenazine and protriptyline. After successful resuscitation and clinical stabilization, cardiac electrophysiologic studies were performed before and after the administration of each of these medications. Perphenazine widened the ventricular echo zone and facilitated induction of short salvoes of ventricular tachycardia (repetitive ventricular response). Protriptyline also widened the ventricular echo zone and allowed easy induction of long runs of ventricular tachycardia. Both psychotropic agents increased the incidence of ventricular dysrhythmias in this patient. The electrophysiologic study is a useful technique in determining the interaction between psychotropic drugs and life-threatening arrhythmias; it may provide a means of identifying the patients with cardiac disease in whom administration of these agents may be fatal.

Major Depressive Disorder↗
PubMed1978

Reversal of chronic diabetes insipidus during treatment with protriptyline.

We have described a 13-year-old white boy with Ondine's curse, sleep apnea and cataplexy who simultaneously developed progressive hypothalamic neuroendocrine deficiencies requiring replacement therapy. The patient was treated with protriptyline, a nonsedating tricyclic antidepressant, for control of the sleep-related symptoms. An unexpected result was the apparent reversal of his chronic diabetes insipidus by protriptyline, necessitating discontinuation of lysine-vasopressin. Some possible mechanisms of action were discussed.

Adolescent↗
PubMed1984

Structure elucidation of protriptyline photoirradiation products.

Three photoirradiation products of the tricyclic antidepressant protriptyline have been isolated by preparative tlc and identified as the 10,11-epoxide, 10-hydroxy and 10,11-dihydrodiol derivatives of protriptyline by tlc, uv and mass spectroscopy.

Dibenzocycloheptenes↗
PubMed1982

Protriptyline in the treatment of sleep apnoea.

Nine patients with obstructive sleep apnoea were treated with 5 to 20 mg of protriptyline each night for two to 18 months. In four patients, there was dramatic, sustained improvement in symptoms and measured sleep quality and apnoea frequency and duration. There was no improvement in two patients and three developed intolerable side-effects preventing adequate treatment. Apnoea frequency was the only apparent predictor of responsiveness. Those with fewer than 30 episodes of apnoea per hour consistently improved. Only two of four patients with more than 60 episodes per hour improved. These results provide additional evidence that a carefully monitored trial of protriptyline may benefit selected patients with mild to moderate obstructive sleep apnoea.

Adult↗
PubMed1975

Steady-state protriptyline levels in an outpatient population.

The authors measured steady-state protriptylive levels in 12 outpatients undergoing treatment for depression. The steady-state level of protriptyline was surprisingly high compared with levels obtained when other tricyclic antidepressants were prescribed. This finding probably accounts for the effectiveness of protriptyline at low doses and its frequent side effects.

Administration, Oral↗
PubMed1977

Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia.

The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties.

Adult↗