Sertraline Nortriptyline

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. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Solid phase extraction (SPE) has been used to efficiently extract several types of antidepressants, which can then be conveniently analyzed on GC-NPD. One assay extracted and analyzed viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine from whole blood in one procedure (Martinez et al., 2002). The same laboratory analyzed fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiUne, clomipramine, and trazodone in whole blood in one assay (Martinez et al., 2003). SPE has also been used for the simultaneous analysis of TCAs and their metabolites by de la Torre et al. (1998). 

Amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, AT-desmethylclomipramine, fluvoxamine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics... 

Other SSRIs may be selected as an alternative to fluvoxamine in the event that fluvoxamine cannot be used. Sertraline is the first option because of efficacy for pediatric GAD (Rynn et ah, 2001) paroxetine is an option because of controlled treatment data for adolescent depression (Keller et ah, 2000) and OCD (see Chapter 39) and fluoxetine is an option because of controlled treatment data for pediatric depression (Em-slie et ah, 1997). Eorazepam is included as a short acting alternative to clonazepam. Nortriptyline, which is less anticholinergic and thus may be better tolerated, is included as an alternative to IMF... 

FIGURE 39.2 Treatment algorithm for pediatric obsessive-compulsive disorder (OCD). In adjusting cognitive behavior therapy (CBT), increase frequency or intensity, or alter the setting or format, e.g., have it be home based or day treatment. CMI, clomipramine DMI, desipramine NT, nortriptyline SSRI, selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram). 

P450 IID6 -fin women Inhibited by OCs Hydroxylation of nortriptyline and desipramine, haloperidol, clozapine, risperidone, venlafaxine Fluoxetine, fluvoxamine, paroxetine, sertraline... 

With regard to its effects on cognitive performance in the target population, the SSRI sertraline appears to be the most thoroughly studied newer antidepressant. Lane and O Hanlon (1999) listed three controlled clinical studies with fluoxetine and three with sertraline however, all three trials with fluoxetine and one of the trials with sertraline were not sufficiently powered to demonstrate reliable differences between treatments. One of the two adequately powered studies, a comparison between nortriptyline and sertraline in elderly depressed patients (Bondareff et al., 2000 see Box 7.3), supports the notion that antidepressants with anticholinergic action (such as nortriptyline) are similarly... 

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 ... 

About 70% of the patients in both treatment groups completed the trial, with similar therapeutic efficacy (Hamilton Rating Scale for Depression) shown for both compounds. The pattern of adverse events was different, with more patients reporting diarrhea, nausea and insomnia on sertraline, and more patients on nortriptyline... 

The MMSE showed some improvement on sertraline and some minor decline on nortriptyline the difference between treatments was statistically significant (P<0.01). 

The number of items recalled on the shopping list task increased on sertraline and decreased on nortriptyline (PcO.OOl). 

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. 

OFFICIAL NAMES Amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), imipramine (Norfranil, Tofranil), isocarboxazid (Marplan), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil), phenelzine (Nardil), protriptyline (Vivactil), sertraline (Zoloft), thioridazine (Mellaril), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Sur-montil), venlafaxine (Effexor) the herb St. John s wort (Hypericum perforatum) is sold over-the-counter without prescription STREET NAMES Happy pills... 

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

FIGURE 3.2. Protocol for thr STARED project, (a) Level 1 (b) level 2 (c) level 3 (d) level 4. CIT, citalopram SER, sertraline BUP, bupropion VEN, venlafaxine CT, cognitive-behavioral therapy BUS, Buspirone MIRT, mirtazpine NTP, nortriptyline LI, lithium THY, thyroid hormone TCP, tranylcypromine. 

The older tricyclic agents show less than a ten-fold selectivity in inhibiting noradrenaline over that for 5-HT (e.g. desipramine, imipramine, nortriptyline) through amitryptyline. which shows virtually no selectivity, to trazodone, zimelidine and clomipramine, which are somewhat 5-HT selective. The newer Serotonin-Selective Reuptake Inhibitors (SSRIs) show a higher selectivity for inhibition of 5-HT reuptake in the brain, and have a different pharmacology. Examples clinically used include citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. Experimental agents include 6-nitroquipazine, alaproclate, litoxetine, indatraline and p-CIT. 

CYP2D6 Antidepressants amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, N-desmethyl-clomipramine, fluoxetine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others codeine, opiate, propranolol, dextromethorphan 4 no activity 25% in Caucasians 0%-10% in others 5 no activity 2%-10% in all groups 10 reduced activity 47%-70% in Asians <5% in others 17 reduced activity 25%-40% in blacks 0% in others 2XN increased activity 19%-29% in Arabs and Ethiopians <5% in others... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nefazodone, nortriptyline, paroxetine, pizotifen, protriptyline, rizatriptan, sertraline, sibutramine, sumatriptan, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Simultaneous amitriptyline, chlorpromazine, clomipramine, dothiepin, doxepin, fluoxetine, fluphenazine, haloperidol, imipramine, maprotiline, mianserin, norclomipramine, nordothiepin, nordoxepin, norfluoxetine, nortriptyline, paroxetine, remoxipride, sertraline, sulpride, thioridazine, trazodone... 

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