MAOIs Amitriptyline

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. 

Amitriptyline and imipramine, and the MAOI phenelzine, can be considered second- or third-line drugs for PTSD after SSRIs have failed. Mirtaza-pine and venlafaxine may also be effective. 

Serotonin syndrome Some TCAs inhibit neuronal reuptake of serotonin and can increase synaptic serotonin levels (eg, clomipramine, amitriptyline). Either therapeutic or excessive doses of these drugs, in combination with other drugs that also increase synaptic serotonin levels (such as MAOIs), can cause a serotonin syndrome consisting of tremor, agitation, delirium, rigidity, myoclonus, hyperthermia, and obtundation. 

Many antidepressant drugs have pronounced effects on sleep. Several tricyclic compounds (amitriptyline and others) have sedative actions while others (imipramine and others) are less sedative or even stimulant. Monoamine oxidase inhibitors (MAOIs) have central stimulant effects and may cause insomnia. Specific serotonin reuptake inhibitors (SSRls) and combined serotonin, noradrenaline reuptake inhibitors (SNRIs) can also cause insomnia. 

Note. AMI = amitriptyline DMI = desipramine ECT = electroconvulsive therapy IMI = imipramine MAOI = monoamine oxidase inhibitor T3 = triiodothyronine ... 

Although most physicians avoid the combination of an MAOl with most other antidepressants, a number of reports indicate that MAOIs combined with a TCA can be effective and safe in treatment-resistant patients. This combination should be used only by a physician skilled in their use and familiar with their potential adverse effects and drug interactions. Generally, tertiary amine TCAs have been used in combination with MAOIs. Once the dose of the TCA is established, the MAOl should be slowly added. Never attempt the reverse order without a 2-week delay. It may also be prudent to lower the TCA dose slightly before starting the MAOl. An example might be the addition of phenelzine to amitriptyline, starting with an initial dose of 15 mg and subsequent dose increments weekly as needed. The total dose of an MAOl, used in combination with TCA, is usually lower than when used alone (e.g., 30 to 60 mg per day). When the combination is discontinued, the MAOl should be stopped first. 

MAOIs TCAs-AMITRIPTYLINE CLOMIPRAMINE DESIPRAMINE IMIPRAMINE NORTRIPTYLINE t risk of stroke, hyperpyrexia and convulsions, t plasma concentrations of TCAs, with risk of toxic effects, t risk of serotonin syndrome and of adrenergic syndrome with older MAOIs. Clomipramine may trigger acute confusion in Parkinson s disease when used with selegiline TCAs are believed to also act by inhibiting the reuptake of serotonin and norepinephrine, increasing the risk of serotonin and adrenergic syndromes. The combination of TCAs and antidepressants can t risk of seizures Very hazardous interaction. Avoid concurrent use and consider the use of an alternative antidepressant. Be aware that seizures occur with overdose of TCAs just before cardiac arrest... 

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

Generally, do not use with MAO inhibitors, including f 4 days after MAOIs are stopped do not start an MAOl until 2 weeks after discontinuing amitriptyline, but see Pearls... 

The first TCAs (imipramine and amitriptyline) and MAOIs appeared between 1957 and 1961 (Fig. 19.1). The MAOIs were developed from antituberculosis agents which had been noted to elevate mood. Independently, imipramine was synthesised from the antipsychotic drug chlorpro-mazine and found to have antidepressant rather than antipsychotic properties. Over the next 25... 

MAPI - There was renewed interest in MAOI since their combination with TCA may be the only alternative to the use of EOT for drug-resistant patients.91 EOT was superior to combined phenelzine and amitriptyline in severe depression,92 but phenelzine alone was as effective as amitriptyline in depressed outpatients.93 Caroxazone, an effective antidepressant drug (29), probably acts through reversible inhibition of the two known forms of IfAO (A and B). ... 

MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine... 

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... 

The treatment of MDD corresponds to three stages acute phase, continuation phase, and maintenance phase. The gross treatment options should follow the strategies listed in Scheme 9.3. The following are only suggestions, which are based mainly on specific data from accumulated research. The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are usually considered as first-line treatments. Amitriptyline and clomipramine are second-line treatments. Other tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs) are third-line treatments. 

Traditionally, dysthymic disorder has not been the focus of pharmacotherapeutic interventions, given its chronicity and the presumed non-biological personality variables associated with it. Psychotherapy and psychoanalysis were generally considered the first-choice treatment options, although these treatment modalities have not been well studied in controlled trials. However, as a result of a series of placebo-controlled medical trials, this attitude has been changed. Among the antidepressants found to be superior to placebo are the selective serotonin reuptake inhibitors (SSRIs, with results being evident so far with fluoxetine and sertraline), the tricyclic antidepressants (TCAs) amitriptyline, desipramine, and imipramine (with a 40-60% favorable response), and the reversible and irreversible monoamine oxidase inhibitors (MAOIs) moclobemide and phenelzine, respectively. 

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