Nortriptyline major depression

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Hall SM, Reus VI, Munoz RF, et al Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry 55 683-690, 1998 Hall SM, Humfleet GL, Reus VI, et al Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry 59 930-936, 2002 Hayford KE, Patten CA, Rummans TA, et al Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 174 173-178, 1999... 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

A few modifications of the described methods have been suggested for making nortriptyline [27-32], Nortriptyline is a drug with a relatively short latent period of action. It is practically devoid of sedative effects. It is used in manic-depressive psychoses, in all forms of endogenous depression, and also in major depressive conditions. The most common synonyms of nortriptyline are aventyl, nortrilen, motival, vivactil, and pamelor. 

Seven TCA drugs are available in the United States for treatment of major depression. They are generally categorized as tertiary or secondary amines. Tertiary amines include imipramine (Tofranil), amitriptyline (Elavil), trimipramine (Surmontil), and doxepin (5m-equan). Desipramine (Norpramin), nortriptyline (Pam-elor), and protriptyline (Vivactil) are secondary amines. 

In a double-blind, parallel-group study, Bondareff et id. (2000) compared the SSRI sertraline and the tricyclic compound nortriptyline with regard to their efficacy and safety in a group of 210 outpatients 60 years and older. The patients met the DSM-DI-R criteria for major depressive episode and had a minimum score of 18 on the Hamilton Rating Scale for Depression. Their mean age was about 68 years, most patients were white and about 60% were female the severity of depression was rated as moderate in more than 70% and as severe in more than 20% of the cases. The daily doses of sertraline were between 50 and 150 mg, and those of nortriptyline were 25 100 mg the treatment lasted 12 weeks. In addition to clinical rating scales and self-assessment instruments, patients took the following tests of cognitive performance ... 

Bondareff, W., Alpert, M., Friedhoff, A.J., et al Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life. Am. J. Psychiatry 157, 729-736. 2000. 

Fabre L, Scharf M, Turan M. Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression a clinical study. J Ctin Psychiatry 1991 52[Suppl 6] 62-67. 

Geller B, Cooper TB, Graham DL, et al. Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6 to 12 year-olds with major depressive disorder. J Am Acad Child Adolesc Psychiatry 1992 31 34-44. 

Roberts RL, Joyce PR, Mulder RT, Begg EJ, Kennedy MA. A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J 2002 2 191-196. 

Nortriptyline intoxication secondary to terbinafine has been observed in a woman with a major depressive disorder (214). After rechallenge her serum nortriptyline concentration rose and the serum concentrations of its two hydroxylated metabolites fell. She had a normal genotype for CYP2D6, suggesting that this interaction can occur even in people without reduced CYP2D6 activity. 

A 68-year-old woman developed major depression. A neurological assessment excluded neurological diseases, including Parkinson s disease. After treatment with citalopram, 20 mg/day for 7 days, she developed severe parkinsonism, with rigidity, tremor, and brady-kinesia, and became unable to walk. The citalopram was withdrawn after a further week and nortriptyline was substituted however, 10 days later parkinsonism was still present. Her symptoms eventually responded to cobeneldopa. 

Psychodynamic supportive psychotherapy (n = 107) has been compared with psychotherapy plus medication (n = 101) in patients with major depressive disorder (93). The medications included venlafaxine, selective serotonin reuptake inhibitors, nortriptyline, and nortriptyline plus lithium. Lithium was used as an augmentation strategy in the patients who took lithium and nortriptyline (number not given). There were no differences in outcomes between the two treatment groups. No adverse effects specific to lithium were reported. 

The addition of lithium to other drug therapy has been studied in 92 patients with treatment-resistant major depression taking nortriptyline (97). Non-responders to nortriptyline (n = 35) were randomized to added lithium or placebo there was no significant difference. 

The dibenzapine derivatives are called tricyclic antidepressants and include imipramine (Tofranil), desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactil), and doxepin (Adapin). Amitriptyline is indicated in depression major depression with melancholia or psychotic symptoms depressive phase of bipolar disorder depression associated with organic disease, alcoholism, schizophrenia, or mental retardation anorexia or bulimia associated with depression (see Figure 20). 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

---