Nefazodone Amitriptyline

Van Laar, M.W., Volkerts, E.R., Verbaten, M.N., et al. Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memoiy. Psychophannacology 162, 351-363, 2002. 

FIGURE 2.6 Serotonergic synapse. Serotonin binds to at least seven different receptors. The most relevant are the 5-HTi receptors (1), 5-HT2 receptors (2), and 5-HT3 receptors (3). Antagonists of the 5-HT2 receptor include nefazodone and the majority of atypical antipsychotic drugs. The serotonin transporter (4) pumps serotonin back into the serotonergic neuron, which can be blocked by drugs such as venlafaxine, clomipramine, imipramine, and amitriptyline. 

Sharp T, Bramwell SR, Lambert P, et al Effect of short- and long-term administration of lithium on the release of endogenous 5-HT in the hippocampus of the rat in vivo and in vitro. Neuropharmacology 30 977-984, 1991 Sharpley AL, Cowen PJ Effect of the pharmacological treatment on sleep of depressed patients. Biol Psychiatry 37 85-98, 1995 Sharpley AL, Walsh AES, Cowen PJ Nefazodone—a novel antidepressant— may increase REM sleep. Biol Psychiatry 31 1070-1073, 1992 Shaw DM, Harris B, Lloyd AT, et al A comparison of the antidepressant action of citalopram and amitriptyline. Br J Psychiatry 149 515-517, 1986 Shaw PJ, Ince PG A quantitative autoradiographic study of H-3-Kainate binding sites in the normal human spinal-cord, brain stem, motor cortex. Brain Res 641 39-45, 1994... 

Area of assessment Clinically sedative antidepressants, e.g. amitriptyline, mianserin, trimipramine Less sedative antidepressants, e.g. bupropion, fluoxetin, moclobemide, nefazodone ... 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

A double-blind continuation study has been conducted with mirtazapine. As with venlafaxine and nefazodone, patients in this acute, double-blind, placebo- and active-controlled study with mirtazapine could remain on the double-blind treatment at the end of the initial 6-week efficacy trial and were then followed up for up to 1 year. There was a statistically significant lower risk of relapse (defined as HDRS > 16) on both mirtazapine (18%) and amitriptyline (28%) in comparison with placebo (53%), indicating that mirtazapine has maintenance efficacy (274). More recently, a 40-week, double-blind, placebo-controlled crossover study was performed with mirtazapine (275). Patients maintained on this drug had less than half the likelihood of relapsing than those patients switched to placebo (i.e., 19.7% versus 43.8%, p <0.01). 

The other tertiary TCA that has dual serotonergic-noradrenergic effects, amitriptyline, like imipramine, appears to be consistently effective in anxiety disorders. Newer antidepressants such as mirtazapine, nefazodone, paroxetine, and venlafaxine may also benefit patients with anxiety disorder ( 60, 61, 62 and 63). 

There has been a report of two patients with treatment-resistant PD who responded to treatment with olanzapine added to ongoing treatment with clonazepam (2 mg per day), ketazolam (30 mg per day), and venlafaxine (150 mg per day). The first patient was started on 7.5 mg at bedtime, and 2 weeks later he was much calmer and sleeping well. Olanzapine was increased to 12.5 mg per day, and venlafaxine was replaced with nefazodone up to 60 mg per day. Over the next few weeks, he improved progressively and clonazepam and ketazolam were discontinued. After 4 months, he was free from panic attacks and left his home alone. The second patient had 10 mg olanzapine daily added to ongoing treatment with 75 mg per day amitriptyline and 10 mg per day diazepam. After 2.5 months, she was being given olanzapine and had started going out on her own (126). 

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... 

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... 

DA agonists levodopa, bromocriptine, ropinirole, pramipexole, selegiline AAAD inhibitor carbidopa M-blockers benztropine, trihexiphenidyl MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone... 

Buspirone does not appear to interact with amitriptyline, cimetidine or terfenadine. An isolated report describes mania when an alcoholic patient taking huspirone was given disulfiram. Nefazodone greatly increases huspirone levels. 

An isolated report describes a woman who developed marked and acute hypotension and weakness when desipramine, fluoxetine and venlafaxine were replaced by nefazodone. Isolated cases describe the serotonin syndrome in patients given nefazodone together, or sequentially, with another serotonei c drug (amitriptyline, paroxetine, St John s wort, or trazodone). The manufacturer recommended that nefazodone should not be used with an MAOI or within 14 days of discontinuing an MAOL Note that, due to adverse hepatic effects nefazodone was widely withdrawn from the market. 

Amitriptyline. A woman who had been taking amitriptyline 10 mg at night and thioridazine developed the serotonin syndrome after taking half a tablet of nefazodone (dosage unspecified). ... 

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