Amitriptyline Monoamine oxidase inhibitors

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 ... 

A collaborative VA study (364) found that the addition of imipramine or a monoamine oxidase inhibitor to CPZ did not benefit chronic psychotic patients any more than CPZ alone. Further, the addition of an amphetamine was slightly harmful. This finding has since been replicated in several studies on apathetic schizophrenic patients (365). A study of chronic ambulatory schizophrenics compared amitriptyline plus perphenazine with perphenazine alone ( 366). While they found the combination slightly better in ameliorating depressive symptoms, it was at the cost of a slight increase in patients thought disorder. 

Antidepressants are divided into the following classes the dibenzapine derivatives are called tricyclic antidepressants and include imipramine (Tofranil), desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactil), and doxepin (Adapin). The monoamine oxidase inhibitors are nsed occasionally to treat depression. The hydrazine derivatives consist of isocarboxazid (Marplan) and phenelzine sulfate (Nardil). The nonhydrazine derivatives inclnde tranylcypromine (Parnate). L-Tryptophan is the only member of the monoamine precnrsors nsed to treat depression. The newer and second-generation antidepressants inclnde amoxapine, doxepin, flnoxetine, maprotiline, trazodone, mianserin, alprazolam, and bnpropion (see also Tables 5 throngh 7). 

In the otherwise unmedicated animal, imipramine and its related compounds have even fewer behavioural effects than the monoamine oxidase inhibitors. Such changes as have been recorded, using conditioned avoidance and escape techniques, suggest that behaviourally the drugs resemble the tranquillizers . Chlorpromazine and amitriptyline have similar depressant effects on the electrical activity of the brain, reducing the frequency of the spontaneous rhythms. Amitriptyline has been used for treating patients in whom depression and anxiety occur together. 

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. 

Selective serotonin reuptake inhibitors (SSRIs) are the first-line therapy for PTSD. Efficacy for fluoxetine, paroxetine, and sertraline has been demonstrated in well-designed double-blind placebo-controlled studies to reduce all symptom domains (intrusive recollection, avoidance/numbness, and hyperarousal). - Other treatment options include the tricyclic antidepressants (TCAs) amitriptyline and imipramine and the irreversible monoamine oxidase inhibitor (MAOl) phenelzine, which have been shown to reduce re-experiencing. However, in comparison with SSRIs, TCAs and phenelzine are associated with a higher incidence of side-effects, risk of overdose, and poor compliance. Alprazolam has demonstrated anecdotal efficacy however, regular use of benzodiazepines is not recommended. Benzodiazepines can be used on an as-needed basis for specific symptoms (e.g. sleep disturbances). CBT has shown beneficial effects in relatively well-controlled studies, while the results with exposure therapy are... 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

Metabolic inactivation, whether taking place in the e,r, or at other sites, is often accidentally inhibited by other drugs. Thus many patients have died as a result of the simultaneous administration of an inhibitor of monoamine oxidase (an enzyme present in mitochondria) and an amine drug which is not toxic on its own. These monoamine oxidase inhibitors, such as tranylcypromine 9,47), are prescribed as mood-elevators in depressive illnesses. Until their synergistic properties were realized, they caused many deaths after usually safe doses of amphetamine, pethidine, and amitriptyline, or after the patient had consumed food rich in pressor amines such as tyramine such foods are red wine, meat-extract, yeast-extract, broad beans, and particularly cheese. These are examples of unfortunate synergism, but many favourable cases are known, examples of which will now be given. 

Early antidepressant medications were called tricyclic antidepressants (TCA), exemplified by dothiepin and amitriptyline. However, there are toxicity issues with these medications. The next generation of antidepressants was the monoamine oxidase inhibitors (MAOIs). As their name implies, they inhibit the monoamine oxidase enzyme thereby inhibiting the oxidation of monoamines such as serotonin that act as neurotransmitters. Examples include selegiline (available in transdermal patch form as Emsam , Somerset... 

In a controlled comparison between clomipramine and amitriptyline, the former caused adverse effects more often, especially drowsiness (3). Overdose toxicity is the same as with other tricyclic antidepressants (4) fatal interactions with monoamine oxidase (MAO) inhibitors have been reported (SEDA-18, 16 5). Altogether, toxic effects are not substantially different. 

Viloxazine selectively inhibits the presynaptic reuptake of NE reuptake (approximately half as potent as imipramine) and is a weak inhibitor of mouse brain 5-HT reuptake. No appreciable in vivo inhibition of monoamine oxidase activity was observed. It differed from the TCAs in not exhibiting the TCA adverse-effect profile. Viloxazine produces antidepressant activities both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug. 

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