Imipramine Monoamine oxidase inhibitors

It can be argued that the introduction of lithium salts into the practice of psychiatry in 1949 heralded the beginning of psychopharmacology, as it predated the discovery of chlorpromazine, imipramine, monoamine oxidase inhibitors and resperine. Lithium came into clinical use serendipitously, the Australian psychiatrist Cade having by chance given it to a small group of manic patients and found that it had beneficial effects. 

Grantiiam J, Neel W, BrownR.W. Toxicity reveised. Reversal of imipramine-monoamine oxidase inhibitor induced toxicity hy chlorpromazine. J Kans Med Soc (1964) 65,279-80. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

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. 

Monoamine oxidase inhibitors [NP] Some cases of excitation, hyperpyrexia, mania, and convulsions, especially with serotonergic antidepressants such as clomipramine and imipramine, but many patients have received combination without ill effects. 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

Panic disorder is one of the most prevalent psychiatric disorders in industrialized countries. It is often associated with agoraphobia and has an estimated prevalence of between 1% and 6%. The use of imipramine in the treatment of anxiety by Klein and Fink, and the discovery by William Sargant that monoamine oxidase inhibitors (MAOIs) were effective in the treatment of "atypical depression" over 30 years ago led to the investigation of the efficacy of such treatments in patients with panic disorder. Since that time, such drugs have been shown to attenuate the symptoms of panic in addition to those of phobic avoidance and anticipatory anxiety. As both the... 

Antidepressants were first introduced into the market in the 1950s with the serendipitous discovery of the antidepressant effect of two drugs initially evaluated for other medical uses Iproniazide, a monoamine oxidase inhibitor (MAOI), and Imipramine, a tricyclic antidepressant (TCA). Since then, a whole new generation of chemically and pharmacologically unrelated compounds have been introduced, which appear to be safer and better tolerated due to a more specific mechanism of action. These include selective serotonin reuptake inhibitors (SSRIs), serotonin and... 

A similar sentiment was expressed in a later British textbook of psychopharmacology Antidepressant drugs, like imipramine and the monoamine oxidase inhibitors differ from euphoriant drugs such as amphetamine in that they appear to act specifically against depressive symptoms (Dally 1967, p. 10). 

Some antidepressants—specifically, tricyclics like imipramine (trade name Tofranil) and amitryptiline (trade name Elavil)—are thought to exert their antidepressant effect through inhibition of a reuptake mechanism that sucks back the neurotransmitters from the synapse into the neuron for storage and future use, a process mentioned in Chapter 1. The resulting net effect is an increase of these molecules at the synapse and thus a more robust neurotransmission. A different category of antidepressants—monoamine oxidase inhibitors (MAOIs)—display a different mechanism of action but with the same net effect of increasing norepinephrine and serotonin neurotransmission they inhibit the metabolism (breakdown) of the molecules stored in the neurons, thus creating more abundant supplies for neurotransmission. 

The bulk of literature examining antidepressant use in AD is made up of case reports and uncontrolled studies. Most of these report a favorable response to antidepressants, but several placebo-controlled trials have demonstrated mixed results. Of the antidepressants studied, citalopram, sertraline, clomipramine, and moclobe-mide (a monoamine oxidase inhibitor not marketed in the U.S.) were considered efficacious in at least one study but fluoxetine and imipramine were no better than placebo. It should be noted that citalopram and sertraline have both been studied in other placebo-controlled trials in this population with no difference over placebo. ... 

Imipramine, a substance with a structure similar to the phenothiazines (Figure 5) but varying in that the ring is a dibenzazepine rather than a phenothiazine, was the first active antidepressant of the nonmomoamine oxidase inhibitor series of agents. It, like the monoamine oxidase inhibitors, is effective in less than half the patients treated. Its mode of action is not clearly understood, but there is increasing evidence that it too exerts an effect on catechol amine metabolism (19). Although serious toxic effects have been uncommon, excitement, jaundice, and blood dyscrasias have occurred (17). 

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. 

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... 

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