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PubMed1992

Combination treatment with noradrenalin and serotonin reuptake inhibitors in resistant depression.

Eight cases of resistant recurrent depression were treated with a combination of nortriptyline and a new serotonin reuptake inhibitor, with or without concurrent lithium therapy. Significant improvement was seen in all patients where other drug regimes and ECT had been ineffective. No adverse reactions occurred in any of our patients, seven of whom were elderly. The combination treatment was more effective than individual therapies alone.

1-Naphthylamine↗
PubMed1977

Carotidynia.

Nosologic uncertainty about carotidynia has arisen, in part, because the syndrome was initially classified as an atypical facial neuralgia. More recently, carotidynia has been characterized as a recurring vascular neck pain, often accompanied by carotid tenderness and soft tissue swelling and sometimes by vascular headaches. We now report that drugs useful in the prophylaxis of migraine appear to be effective in carotidynia. Eight women (ages 39 to 77) with unilateral, episodic neck pain of 1 to 19 years' duration have been observed for periods ranging from 7 months to 6 years. All experienced marked relief in the intensity and frequency of their pain syndromes after the administration of methysergide, ergonovine maleate, propranolol, or nortriptyline. No patient had evidence of arteritis. The responsiveness of both migraine headaches and carotidynia to similar drugs suggests a common pathophysiologic mechanism.

Adult↗
PubMed1992

Pharmacokinetic analysis of amitriptyline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of amitriptyline.

The compartmental model analysis by use of simultaneous curve fitting was carried out to ascertain the pharmacokinetic relationship between amitriptyline (AMT) and nortriptyline (NRT) in the serum and brain after acute or chronic oral administration of AMT. The estimated F value, a fraction of dose reached at systemic circulation, and the MD value, a fraction metabolized to NRT, were 0.044 and 0.020, respectively, after acute administration, indicating first-pass metabolism of AMT. The estimated parameters kin and kout, the transfer rate constants to and from the brain, showed no marked difference between AMT and NRT. These findings indicate equivalent ability of AMT and NRT to penetrate into the brain. The area under the concentration curve (AUC) values of AMT and NRT in the serum increased 1.4 and 8.2 times, respectively, with the increase of NRT being greater after chronic administration. The MD value was increased from 0.020 to 0.096, whereas the estimated F value showed no marked change. These results indicate the enhanced first-pass metabolism. The estimated transfer rate constants kin and kout of AMT were close to those of NRT. In addition, the transfer rate constants after chronic administration were similar to those after acute administration, indicating no marked change in penetration into the brain by multiple dosing.

Administration, Oral↗
PubMed2005

Diurnal panic attacks with and without nocturnal panic attacks: are there some phenomenological differences?

OBJECTIVE: To compare nocturnal and diurnal panic attacks in a cross-sectional study and in a longitudinal prospective short-term follow-up. METHODS: We selected 57 panic disorder (PD) subjects (DSM-IV) and rated them with the Panic Disorder Severity Scale (PDSS) at baseline and after 30 days of treatment with nortriptyline, and with the Eysenck Personality Inventory and the Brown Attention Deficit Disorder (ADD) Scale at baseline. RESULTS: The sample was divided into a nocturnal and diurnal panic attack (NDPA) group--57.9% (n = 33)--and a diurnal panic attack (DPA) group--42.1% (n = 24). The groups showed a similar mean age at onset of PD and a pattern of prominent respiratory symptoms. The PDSS did not differ between the groups following short-term treatment (p = 0.451). There were also neither significant differences in Neuroticism (p = 0.094) and Extroversion (p = 0.269) nor in the Brown ADD Scale (p = 0.527). CONCLUSION: In our study, patients with both nocturnal and diurnal panic attacks showed similar features in their phenomenology and short-term outcome when compared to pure diurnal panic attacks patients.

Adolescent↗
PubMed2001

Effect of nonnicotine pharmacotherapy on smoking behavior.

Smoking-related disease is the single biggest preventable cause of morbidity and mortality in the United States, yet approximately 25% of Americans continue to smoke. Various dosage forms of nicotine replacement therapy increase smoking quit rates relative to placebo, but they generally do not result in 1-year quit rates of over 20%. To increase these rates, a number of nonnicotine agents have been investigated. Drugs that modulate noradrenergic neurotransmission (bupropion, nortriptyline, moclobemide) are more effective than those affecting serotonin (selective serotonin reuptake inhibitors, buspirone, ondansetron) or other neurotransmitters.

Amphetamines↗
PubMed1976

Rating scales as predictors of response to tricyclic antidepressants.

Fifty-three patients suffering from depressive illness were classified as 'responders' or 'non-responders' on the basis of an "amelioration score" of the Hamilton Rating Scale for depression after six weeks treatment with nortriptyline hydrochloride at 150 mgs. daily. A multivariate analysis of variance was performed on the four psychological rating scale scores used, to determine whether rating scales could predict treatment response to tricyclis antidepressants was found to be at 75% probability.ic anti-depressants was found to be at 757. probability.ic antidepressants. There was a significant difference between the two groups after adjustment for age. Subjects were then classified as 'non-responders' and 'responders' on the basis of their discriminant scores. The prediction of response to tricycl

Adult↗
PubMed1994

Bupropion/nortriptyline combination for refractory depression.

Many patients fail to respond to one or more trials with a single antidepressant. In such cases polypharmacy is often necessary and beneficial, although there may be an increased risk of complications. Four case reports are presented of patients with refractory depression treated successfully with the combination of the tricyclic antidepressant nortriptyline and the newer agent bupropion.

Bupropion↗
PubMed2004

Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors.

BACKGROUND: Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR). METHOD: Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks. RESULTS: Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects. CONCLUSION: We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.

Aged↗
PubMed1999

Treatment of depression in patients with heart disease.

Patients with depression are more likely than patients without depression to develop ischemic heart disease and suffer cardiac-related death. Recent evidence suggests that the association between depression and increased cardiac mortality may in part be due to an increase in platelet activity and an imbalance in sympathetic and parasympathetic activity that makes the patient more susceptible to ventricular fibrillation. Available data suggest that the tricyclic antidepressants (TCAs) may increase the risk of mortality in patients with ischemic heart disease. Three studies with the selective serotonin reuptake inhibitors (SSRIs), including a double-blind, randomized comparison of paroxetine with nortriptyline, support the conclusion that the SSRIs have a relatively benign cardiovascular profile. Therefore, they are preferable to the TCAs for treatment of depression in patients at risk for cardiac events. Additional studies are needed to definitively establish the cardiovascular safety of the SSRIs.

Antidepressive Agents, Second-Generation↗
PubMed1975

Anxiety/depression in elderly patients. A double-blind comparative study of fluphenazine/nortriptyline and promazine.

A double-blind study involving sixty-two patients, aged 65 years or over, treated for twenty-eight days, showed that fluphenazine 0-5 mg/nortriptyline 10 mg three times daily was superior to promazine 50 mg three times daily in relieving symptoms of anxiety and was associated with a lower incidence of side-effects. The results are discussed in the light of the nature of anxiety/depression syndromes in the elderly and it is suggested that since symptoms of anxiety in these disorders are often manifestations of an underlying depressive illness, the antidepressant effect of the nortriptyline may have enhanced the 'anxiolytic' advantage of fluphenazine/nortriptyline.

Age Factors↗
PubMed2000

Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression.

Twenty elderly outpatients with major depression were treated with either nortriptyline or sertraline. Resting regional cerebral blood flow (rCBF) was assessed by the planar (133)Xenon inhalation technique after a medication washout and following 6- 9 weeks of antidepressant treatment. At baseline, the depressed sample had reduced rCBF in frontal cortical regions when compared with 20 matched normal-control subjects. After treatment, Responders and Nonresponders differed in the expression of a specific topographic alteration, with Responders manifesting reduced perfusion in frontal regions. These findings are consistent with this group's previous report of reduced rCBF after response to electroconvulsive therapy (ECT) and suggest a common mechanism of action.

Aged↗
PubMed1975

Interactions of tricyclic antidepressants and barbiturates in barbiturate-tolerant and nontolerant rats.

Pretreatment of rats with tricyclic antidepressants, imipramine, desipramine, amitriptyline and nortriptyline, at two doses (5 and 25 mg/kg) 20 minutes before administration of barbiturate markedly reduced the latent period of the response to barbital and prolonged the sleeping time induced by pentobarbital (PB) and barbital. The effects were dose-dependent. The prolonged sleeping time produced by PB was associated with decreases in the rates of disappearance of PB from the brain and plasma. The effect of tricyclic antidepressants on PB hypnosis in PB-tolerant and nontolerant rats was apparently not related to change in central nervous system (CNS) sensitivity to PB, since at the time of awakening there were no significant differences in the concentrations of unmetabolized PB in either the plasma or brain of tricyclic antidepressant-treated animals as compared to controls. As barbital is not metabolized, potentiation of barbital hypnosis by tricyclic antidepressants must be attributable to a direct effect on CNS rather than on liver microsomal enzymes. Direct evidence was provided by the findings that amitriptyline accelerated the brain uptake of barbital and that amitriptyline-treated animals lost and recovered the righting reflex at brain barbital levels lower than those of controls. Rats made tolerant to the hypnotic effect of barbital also became tolerant, in varying degrees, to the hyposis-prolonging properties of tricyclic antidepressants. It is concluded that tricyclic antidepressants prolong PB sleeping time in PB-tolerant and nontolerant rats by inhibiting its biotransformation in the liver. The action of tricyclic antidepressants to prolong the hypnotic action of barbital in normal rats is related to their direct effects on CNS sensitivity to barbital, but such effects are makedly diminished after animals become tolerant to barbital.

Amitriptyline↗
PubMed1975

Drug induced biogenesis of nitrosamines.

It has been demonstrated that potentially corcinogenic nitroso compounds are readily formed when certain widely used drugs with secondary alkylaminostructures (e.g. nortriptyline and fenfluramine) or drug metabolities with such structures (e.g. norpropoxyphene) are reacted with nitrite in dilute acid aqueous medium or in human gastric juice under simulated gastric conditions. The reactions occur so readily in vitro that new quantitative procedures for the determination of these drugs have been developed and based on these principles. The potential hazards associated with the long term clinical use of such drugs are discussed.

Carcinogens↗
PubMed2002

Managing nicotine addiction.

Nicotine addiction has been identified as the primary contributor to continued widespread tobacco use worldwide. Although the health benefits of smoking cessation are well publicized, few smokers successfully quit on a long-term basis. A number of pharmacological agents have been shown to approximately double long-term smoking cessation rates and have, therefore, been recommended as first-line therapy for the treatment of nicotine dependence in the clinical practice guidelines recently released by the Agency for Healthcare Research and Quality (AHRQ). These include the currently available dosage forms of nicotine replacement therapy (gum, patch, nasal spray, and inhaler) and bupropion. Other agents that have exhibited some efficacy in increasing smoking cessation rates are nortriptyline and clonidine. All pharmacological treatments are most effective in conjunction with behavioral therapy. Other approaches to treating tobacco use disorder now being investigated include additional ways to administer nicotine, a vaccine to prevent nicotine from crossing the blood-brain barrier, and agents that alter the metabolism of nicotine. This review summarizes the characteristics of nicotine addiction, reviews the pharmacological agents currently used to treat tobacco use disorder, and describes possible approaches to treat nicotine dependence in the future.

Administration, Inhalation↗
PubMed1992

Drug-induced Creutzfeldt-Jakob like syndrome.

A patient with progressive neurological deterioration characterized by cognitive impairment, myoclonus, Parkinson's syndrome, an abnormal electroencephalogram and fasciculations was considered for brain biopsy for suspected Creutzfeldt-Jakob disease. Complete clinical recovery followed discontinuation of lithium and nortriptyline. Awareness of this unusual drug-induced Creutzfeldt-Jakob like syndrome can avoid costly, invasive and unnecessary investigative procedures.

Creutzfeldt-Jakob Syndrome↗
PubMed1992

Brief communication. Vitamin B1, B2, and B6 augmentation of tricyclic antidepressant treatment in geriatric depression with cognitive dysfunction.

This was a 4-week randomized placebo-controlled double-blind study to assess augmentation of open tricyclic antidepressant treatment with 10 mg each of vitamins B1, B2, and B6 in 14 geriatric inpatients with depression. The active vitamin group demonstrated significantly better B2 and B6 status on enzyme activity coefficients and trends toward greater improvement in scores on ratings of depression and congnitive function, as well as in serum nortriptyline levels compared with placebo-treated subjects (Ss). Without specific supplementation, B12 levels increased in Ss receiving B1/B2/B6 and decreased in placebo Ss. These findings offer preliminary support for further investigation of B complex vitamin augmentation in the treatment of geriatric depression.

Aged↗
PubMed1992

Molecular structure and dynamics of the four 10-hydroxynortriptyline isomers.

The three-dimensional structures, molecular conformations, and electrostatic potentials of the R-E-, S-E-, R-Z-, and S-Z-isomers of 10-hydroxynortriptyline were examined by computer graphics, molecular mechanical energy calculations, and molecular dynamics simulations in vacuo and in aqueous solution. Molecular models of the isomers, based on the structure of nortriptyline, were refined by energy minimization and used as starting points in the simulations. R-E- and S-Z-10-hydroxynortriptyline formed intramolecular hydrogen bonds between the side-chain nitrogen atom and the hydroxyl group during the simulations in vacuo, and had the side chain folded over the ring system in the minimum energy conformations. Intramolecular hydrogen bonding was not observed for R-Z- and S-E-10-hydroxynortriptyline, which had extended side chains in the minimum energy conformations and stronger negative molecular electrostatic potentials around the hydroxyl group than the R-E- and S-Z-isomers.

Models, Molecular↗
PubMedDate not supplied

Persistent idiopathic facial pain following dental implant placement: a case report.

The present case report depicts the management of a patient with persistent idiopathic facial pain following the placement of 2 dental implants in the mandibular anterior alveolar ridge. After 15 months of unsuccessful diagnosis and management, the patient was seen at the Orofacial Pain Unit of the Oral Surgery and Implantology master's degree program of the University of Barcelona. Seven months after treatment onset, a combination of nortriptyline, clonazepam, and relaxation procedures has successfully controlled the patient's facial pain symptoms.

Analgesics↗