Depression amitriptyline

Hollister LE, Overall JE, Shelton J, et al. Drug therapy of depression. Amitriptyline, perphenazine, and their combination in different syndromes. Arch Gen Psychiatry 1967 17 486-493. 

Traditional local anaesthetics (lidocaine), antiarrhythmics (mexiletine) and anticonvulsants (phenytoin), antipsychotics (carbamazepine) and anti-depressants (amitriptyline) have all been used clinically, with substantial interpatient... 

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Mr. Hopkins has been severely depressed for several months. Two weeks ago the primary care provider prescribed amitriptyline 30 mg orally four times a day. His family is concerned because he is still depressed. They are requesting that the dosage be increased. Discuss what information you would give Mr. Hopkins and his family and what assessments you could make... 

SkaerTL, Sclar DA, Robison LM, et al (1995). Economic valuation of amitriptyline, desipramine, nortriptyline, and sertraline in the management of patients with depression. Curr Ther Res 56, 556—67. 

Doxepine, Amitriptyline, Imipramine, Iproniazid, Pheniprazine Depression and anxiety... 

Chen, L. X., Wang, Z. G., Ai, M. et al. (2005). Effect of CYP2C19 genotypes on demethylation of amitriptyline in Chinese patients with depression. Chinese Journal of Nervous and Mental Diseases, 31(1), 33-6. 

Versiani, M., Ontiveros, A., Mazzotti, G., Ospina, J. et al. (1999). Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression) a doubleblind comparison. Int. Clin. Psychopharmacol, 14, 321-7. 

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). 

Dopaminergic neurons depression Mouse nucleus accumbens dopaminergic neurons Amitriptyline time course Markers for adaptive response to anti-depressant therapy [21]... 

Tricyclic Antidepressants (TCAs). Because of their effectiveness not only for depression but for anxiety disorders such as panic disorder as well, TCAs were the first medications formally tested in the treatment of PTSD. Three TCAs, amitriptyline, imipramine, and desipramine, have been studied in small trials, producing modest benefit for reexperiencing and hyperarousal symptoms, without any relief of avoidance/numbing symptoms. Given this limited benefit in conjunction with the side effect burden and potential for toxicity in a suicide prone population, TCAs are infrequently used in the treatment of PTSD. Please refer to Chapter 3 for more information regarding TCAs. 

Tricyclic Antidepressants (TCAs). The TCAs have been nsed to treat ADHD for 30 or more years. Most often used are imipramine (Tofranil) and desipramine (Norpramin), mainly becanse they are the TCAs that most specihcally increase norepinephrine activity. Remember, boosting norepinephrine activity in the brain shonld improve attention. Other TCAs, namely, amitriptyline (Elavil, Endep) and nortriptyline (Pamelor), have been used, though they also increase norepinephrine activity. TCAs do offer a modest benefit for both the inattention and the hyperactivity of ADHD. In addition, they are often effective at doses mnch lower than those required to treat depression. However, their effectiveness nsnally falls short of the stimulant medications. In addition, TCAs have considerable side effects including dry mouth, constipation, drowsiness, weight gain, and adverse cardiac effects. 

When treating insomnia without depression, doxepin and amitriptyline (both tricyclic antidepressants) can be administered in low doses (25-100 mg) at bedtime. These antidepressants, however, do have troublesome anticholinergic side effects (dry mouth, constipation, blurred vision, dizziness) and adverse effects on the heart, and they can be lethal if taken in overdose. Because of their effect on heart function, these antidepressants should be avoided in patients with heart problems and administered cautiously, if at all, to those who are already receiving one of any number of newer antidepressants that inhibit the metabolism of the TCAs. 

Apart from the antidepressant effect, acute effects occur that are evident also in healthy individuals. These vary in degree among individual substances and thus provide a rationale for differentiated clinical use (p. 233), based upon the divergent patterns of interference with amine transmitters/modula-tors. Amitriptyline exerts anxiolytic, sedative and psychomotor dampening effects. These are useful in depressive patients who are anxious and agitated. 

Certain tricyclic compounds are found to be powerful stimulants, or antidepressants, to the central nervous system. Depressed individuals may respond with an elevation of mood, increased physical activity, mental alertness, and an improved appetite. Imipramine and amitriptyline hydrochlorides are good examples. 

Activity in these tricyclic compounds is restricted to compounds having a two- or three-carbon side chain and methyl-substituted or unsubstituted amino groups in the side chain. Some compounds with substituents on the aromatic ring are active. Finally, the two-carbon bridge linking the aromatic rings may be -CH2—CH2— or -CH=CH—. Amitriptyline is recommended for the treatment of mental depression, with improvement in mood seen in two to three weeks after the start of medication. Imipramine is used in similar cases. 

Amitriptyline is used for anxious-depressive conditions. It is easier to tolerate than imipramine. The most frequently encountered synonyms are triptizol and amiprin. 

Protriptyline is a powerful antidepressant, the mechanism of action of which is not known. It is not a MAO inhibitor and does not stimulate the CNS. It begins to act much faster and acts much longer than imipramine or amitriptyline. Protriptyline does not possess sedative tranquilizing properties. It is used in clinical conditions for treating severe depression. The most common synonyms are concordin, triptil, and vivactil. 

The antidepressant action of amoxapine is comparable to that of imipramine and amitriptyline. It exhibits antagonistic activity on dopamine (D2) receptors. Amoxapine is intended more for relieving symptoms in patients with neurotic or situational depression. It has a number of serious side effects. Synonyms of this drug are asendin, amoxan, moxadil, and others. 

Topiramate may affect alcohol, amitriptyline, CNS depressants, lithium, oral contraceptives, digoxin, estrogens, hydantoins, metformin, risperidone, and valproic acid. 

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