Use Of Monoamine Oxidase Inhibitors Research Articles

Phenelzine use throughout pregnancy and the puerperium: Case report, review of the literature, and management recommendations

Little is known about the use of monoamine oxidase inhibitors (MAOIs) during pregnancy and the postpartum period. We present a literature review with what we believe is the second case report of phenelzine exposure throughout pregnancy and the postpartum period. Potential indications for use and principles of the clinical management of the pregnant patient treated with an MAOI are also discussed and include: documenting informed consent, MAOI dose adjusting during pregnancy, monitoring of maternal and fetal outcome, and appropriate analgesia and anesthesia during labor and delivery. Our patient tolerated phenelzine well throughout her pregnancy but experienced recurring depressive symptoms during periods of significant weight gain requiring dose adjustment. Labor, delivery, and the perinatal period progressed without complication for our patient and her infant, in whom no congenital malformation was detected. Additional case reports and animal studies of MAOI use during gestation may help determine safety and refine clinical management guidelines.

Ketorolac and propofol anesthesia in a patient taking chronic monoamine oxidase inhibitors

There is continued controversy regarding the concurrent use of monoamine oxidase inhibitors (MAOIs) and opioids in anesthesia. MAOIs are being used in both psychiatry and also in the treatment of Parkinson's disease. The adverse interaction of meperidine with MAOIs is well described in the literature. Several other opioids used in anesthesia have been reported as potentially safe and also implicated in interaction with MAOIs. We present a case report using ketorolac as a nonopioid analgesic during a general anesthesia combined with midazolam and propofol in a successful approach in a patient continuing MAOI therapy.

Monoamine Oxidase Inhibitors

After initial enthusiasm, the use of monoamine oxidase inhibitors (MAOIs) has been limited by the wide range of MAOI-drug and MAOI-food interactions that are possible, particularly with sympathomimetic medications or tyramine-containing foods, resulting in hypertensive reactions. Despite their clinical benefits, this has led to a reduction in use of such medications. Discovery of the 2 main subgroups of monoamine oxidase, types A and B, led to the synthesis of MAOIs selective for one or other of these isoenzymes. Consequently, selegiline (deprenyl), a selective MAO-B inhibitor, was developed for the treatment of idiopathic Parkinson's disease. This drug is useful in the treatment of the early stages of the disease and later on as an adjunct to other drug therapies. Although the selective MAO-A inhibitor, clorgiline (clorgyline), was found to be effective in the treatment of depression, it still retained the potential to cause hypertensive reactions. Recently, agents that are not only selective, but reversible in their inhibition of MAO-A (RIMAs) have been synthesised (e.g. moclobemide and toloxatone), and have proven antidepressant efficacy. Whilst they are less likely to induce hypertensive reactions with the concomitant administration of sympathomimetic drugs or with tyramine-rich foodstuffs, it still seems wise to advocate care in co-prescribing potentially interacting medications and to advise a degree of caution with regard to the dietary intake of foodstuffs likely to contain a high tyramine content. Although these newer drugs represent an advance in safety, their use has, as yet, only been established in the treatment of depression. RIMAs also retain a potential for adverse interaction with other drugs. Concomitant prescription of serotonin-enhancing drugs should only be undertaken with caution for patients on moclobemide, toloxatone or selegiline. Coprescription of sympathomimetic drugs should also be avoided with these newer MAOIs and patients should be advised against purchasing over-the-counter preparations that may contain sympathomimetic drugs.

Atypical depression: clinical aspects and noradrenergic function.

The authors assessed the frequency of atypical depression in depressed outpatients and compared clinical and biological features of patients with atypical and nonatypical depression. Depressed outpatients (N = 114) were diagnosed with the Schedule for Affective Disorders and Schizophrenia (SADS) according to Research Diagnostic Criteria. Patients were assessed for presence or absence of atypical depression with the Atypical Depressive Disorder Scale. Atypical depression was defined as the presence of mood reactivity during the depressive episode, along with at least one of four associated features: hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity. All patients completed the SCL-90 and were rated with the Hamilton Depression Rating Scale, extracted from the SADS. To assess biological functioning, the authors examined cortisol response to 75 mg of desipramine, a relatively selective norepinephrine reuptake inhibitor. Twenty-nine percent of patients met criteria for atypical depression. Patients with atypical depression were significantly more likely to be female. Patients with atypical and nonatypical depression did not differ on SCL-90 subscale scores. Although extracted Hamilton depression scale scores were significantly higher for patients with nonatypical depression, the difference was not clinically significant. Patients with atypical depression exhibited a significantly different cortisol response to desipramine injection than patients with nonatypical depression, which suggested that nonatypical depression may be associated with a more impaired norepinephrine system. In view of data in this study, as well as earlier studies, atypical depression has a unique symptom profile, may be widely prevalent, has a distinct treatment response, and may indicate a less impaired biological system than nonatypical depression. Since this is the first report to evaluate the frequency of atypical depression as well as the norepinephrine system in atypical depression, this study needs to be replicated. Nonetheless, the data support the inclusion of atypical depression as a subtype of the depressive disorders in DSM-IV.

Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies.

Monoamine neurotransmitters are important in the development of the immature mammalian brain, prior to assuming their role as neurotransmitters. The endogenous levels of these transmitters are highly regulated by the enzyme monoamine oxidase (MAO). Thus, any change in this enzyme should have a profound effect on brain development. In order to test this hypothesis, we treated developing rat pups with the monoamine oxidase inhibitors (MAO-Is), clorgyline (MAO-A, 3 mg/kg), and deprenyl (MAO-B, 3 mg/kg) throughout gestation (MAO-I-birth), or throughout gestation and to sacrifice (MAO-I-sac). The animals were analyzed for serotonin and dopamine terminal density, using 3H-paroxetine and 3H-GBR 12935, respectively. Whereas there were no changes in the development of the dopamine system, the serotonin system was severely affected, particularly in the cortex that showed a significant reduction of innervation at 30 days postnatal. The animals reached all normal development milestones on schedule, and had no changes in measures of anxiety (% light/dark); however, the animals showed increased open field activity and deficits in a passive avoidance paradigm, which may be a measure of impulsivity. The MAO-I-sac animals were severely impaired, showing stereotypic behavior, seizures, and eventually visual impairments. Our results are discussed in terms of relevance to human disease states, such as atypical Norrie's disease, impulsivity, and hyperactivity. As well, our results should be used to caution against the use of MAO-Is in women of child-bearing age.

Isoniazid and antidepressants

The antituberculous drug isoniazid has weak monoamine oxidase inhibiting properties. Drug and dietary restrictions generally applied to the use of monoamine oxidase inhibitors (MAOI) have not been routinely recommended with its use. Here we report three cases in which antidepressant drugs and isoniazid were co-administered. In two, adverse events, possibly due to an interaction between the drugs prescribed are described. We suggest that the combination of isoniazid and antidepressants be used with caution until further data are accumulated.

Monoamine oxidase inhibitors and elective surgery.

Monoamine oxidase inhibitor use is considered a contraindication for elective surgery. We reviewed 32 patients on a regimen of isocarboxazid 10 mg daily who underwent elective surgery. Their anesthetic management, postanesthesia outcome, and pharmacology are described.

Monoamine oxidase inhibitor use is declining

Monoamine oxidase inhibitor use is declining

Are the Monamine Oxidase Inhibitors Facing Extinction?

The use of monoamine oxidase inhibitors (MAOIs) in the province of Saskatchewan was compared for two years, 1978 and 1986, using the Saskatchewan Prescription Drug Plan data base. The percentage of the adult population receiving an MAOI decreased from 0.17% in 1978 to 0.07% in 1986. The use of both tricyclic antidepressants and the new generation antidepressants increased during the same period. Physicians appear to have selectively avoided using MAOIs for the elderly. Physicians who are not psychiatrists showed the greatest reduction in their use of the MAOIs. The data indicate an increasing reluctance to prescribe the MAOIs despite the recent resurgence of interest in these agents and the positive literature concerning their safety and efficacy.

Evaluation of the effects of inhibition of monoamine oxidase and senescence on methamphetamine-induced neuronal damage

The administration of high doses of methamphetamine causes long lasting damage to central dopaminergic and serotonergic neurons through a mechanism known to involve presynaptic, cytoplasmic stores of those transmitters and thought to be dependent upon a free radical reaction. The following studies were designed to determine if differential inhibition of the subtypes of monoamine oxidase would alter the magnitude of the methamphetamine induced neuronal damage. In addition, since monoamine oxidase type B increases with age, the effects of high dose administration of methamphetamine were evaluated in sensescent mice. It was observed that inhibition of monoamine oxidase type A, and to a lesser degree, type B, increased the magnitude of methamphetamine-induced neuronal damage and that aged mice were more sensitive to the toxic action of methamphetamine. These results are interpreted with respect to the use of monoamine oxidase inhibitors in the treatment of Parkinson's disease.

Dietary Restriction, Tyramine, and the Use of Monoamine Oxidase Inhibitors

The aim of this study is to provide clearer guidelines for rational, safe, and practical dietary restriction for use with monoamine oxidase inhibitors. Tyramine levels were assayed in over 100 of the controversial foods that have been associated with hypertensive reactions or reported to contain high levels of tyramine. Only a very limited number of foods appear to require absolute restriction. These include all aged cheeses, concentrated yeast extracts (e.g., Marmite), sauerkraut, and broad bean pods. Alcoholic beverages, including Chianti wine consumed in moderation, appear to be safe. Some aged meats contain relatively high levels of tyramine and require closer investigation.

A European Study of Views on the Use of Monoamine Oxidase Inhibitors

A total of 1269 psychiatrists, from 15 European countries, completed a questionnaire assessing treatment choice in depressive and anxiety disorders, with particular focus on diagnostic and other factors determining use of monoamine oxidase inhibitors (MAOIs). Tricyclic and similar antidepressants were used most commonly--MAOIs were used as first-choice therapy for depressive or anxiety disorders only by a minority but were commonly a second-choice treatment for atypical depressives. Use was inhibited by interactions and side-effects rather than by perceived ineffectiveness. Cross-national differences in treatment were considerable but diagnostic differences in case history vignettes were much smaller.

Acute Cardiovascular Response to Monoamine Oxidase Inhibitors

Despite the widespread use of monoamine oxidase inhibitors (MAOIs) and the well-known adverse event of hypertensive crisis, few studies have addressed the acute cardiovascular response to an MAOI dose. We prospectively measured pulse and blood pressure changes just before and at 1, 2, 3, and 4 hours after MAOI administration in 18 patients. Significant but asymptomatic increases from baseline in mean systolic and diastolic blood pressure occurred within 2 hours after MAOI administration, with return to near baseline by 4 hours. The mechanism of this reaction is unknown.

Monoamine oxidase inhibitors: safety and efficacy issues.

Controversy has historically centered on the use of monoamine oxidase inhibitors (MAOI) in the treatment of depression because of safety and efficacy issues. Hypertensive crisis following ingestion of foods containing tyramine is the most feared problem associated with MAOI therapy. The authors conclude that only four tyramine-containing foods clearly warrant absolute prohibition, but indicate situations where moderation should apply. Although MAOI remain second-line agents in the treatment of endogenous depression, it is unclear whether MAOI or tricyclic antidepressants should be the drugs of choice in atypical depression and this question necessitates future research.

Cardiac myonecrosis in hypertensive crisis associated with monoamine oxidase inhibitor therapy

A young woman taking tranylcypromine for depression was hospitalized with severe chest pain and hypertension after eating cheese. Electrocardiography initially showed arrhythmias and precordial ST segment depression. Myocardial creatine kinase values were elevated, and echocardiography showed regional ventricular dysfunction, suggestive of focal cardiac myonecrosis. The cardiovascular pathophysiology of tyramine hypertensive crisis and related catecholamine excess states, including pheochromocytoma and clonidine withdrawal, is reviewed. Cardiac myonecrosis is a potential adverse effect of the hypertensive crisis associated with monoamine oxidase inhibitor use. Psychiatric indications for monoamine oxidase inhibitors may be expanding, but clinicians should continue to exercise caution in the use of these agents.

Monoamine Oxidase Inhibitors and Narcotic Analgesics

There has been a recent renewal of interest in the use of monoamine oxidase inhibitors, but the concurrent administration of narcotic analgesics is often a cause for concern. This review clarifies the different types of MAOI/narcotic interactions and offers guidelines for the use of narcotic analgesics in the presence of MAOIs. The MAOI/pethidine interaction has two distinct forms: an excitatory and a depressive form. Pethidine must never be used in the presence of MAOIs because of the risk of a fatal excitatory interaction. Morphine does not cause this excitatory interaction, and is the drug of choice provided an allowance is made for possible potentiation of the depressive narcotic effect. It is inevitable that strong analgesia will occasionally be required as an emergency measure in patients on MAOIs, and insufficient attention is paid in psychiatric textbooks to the two different types of interactions and their therapeutic implications.

Vasopressor challenges during chronic MAOI or TCA treatment in anesthetized dogs

Ten male mongrel dogs were treated in Phase I with tranylcypromine, 6 mg/kg IM b.i.d., for 21 days. Dogs were anesthetized at weekly intervals before, during, and up to four weeks after drug treatment with a combination of amylbarbital, 25 mg/kg, 1% enflurane in 70:30 N 20:0 2) and fentanyl, 500 mcg. Bolus IV injections of norepinephrine, 0.1–0.6 mcg/kg, and ephedrine, 0.03–0.12 mg/kg were given while continuously recording arterial blood pressure, lead II of the ECG, heart rate, and rectal temperature. Awakening times were noted. In Phase II, the dogs were given imipramine, 25 mg/kg IM b.i.d., for 21 days. During Phase III, 14 days of tranylcypromine, 7 days of tranylcypromine plus imipramine, and 7 days of imipramine were administered. Anesthetic techniques were repeated in phases II and III. The fourth phase consisted of tranylcypromine injections, 6 mg IM b.i.d., and anesthesia with amylbarbital 25 mg/kg, 2.5% enflurane in 70:30 N 20:0 2. Vasopressor challenges were repeated during each phase of the study. Following induction of anesthesia and prior to fentanyl challenge, baseline blood pressures and heart rates did not differ from control in Phase I, II, and III of this study. Responses to norepinephrine during all of the tranylcypromine phases were not significantly different from control but ephedrine responses were prolonged, peaking by the second week of treatment. During Phase II, dysrhythmias occurred following norepinephrine and ephedrine with one lethality following norepinephrine, 0.2 mcg/kg. Responses to norepinephrine and awakening times were significantly greater during Phase II compared to Phase I. In Phase III, during the first week of combined therapy the responses to norepinephrine were significantly greater than any other week of this phase. During Phase IV, resting blood pressure and the ephedrine responses were significantly increased during tranylcypromine when the anesthesia regimen did not include fentanyl. These results suggest that during initial treatment with tranylcypromine or imipramine, cardiovascular responses to vasopressor challenges were predicted by the pharmacology of the antidepressant. During tranylcypromine phases, we did not observe exaggerated cardiovascular effects during anesthesia and vasopressor challenges as had been previously reported. The use of monoamine oxidase inhibitors (MAOIs), alone or in combination with tricyclic antidepressants (TCAs), has been increasing over the last few years because they appear to be more effective than TCAs alone in treating resistant affective disorders. (1,2) However, reluctance to use MAOIs has persisted because of reports of interactions with various foods and drugs. (3–6) In recent years, cell membrane receptor studies have shown that chronic treatment (greater than 14 to 21 days) with either MAOIs of TCAs results in physiological adaptations that partially reduce the interactions between drugs and their receptors. (7,8) Attenuation of arrhythmogenicity has been described in dogs after six weeks of TCA treatment. (9) Clinically, patients on chronic MAOI therapy have undergone elective surgery, including open-heart surgery, without adverse responses. (10,11) The cardiovascular response to analgesics, anesthetics, and vasopressors during the initial phase (less than 14 to 21 days) of treatment with MAOIs compared to TCAs has yet to be addressed. Therefore, the purpose of this study was to examine the cardiovascular responses of analgesic, anesthetic, and vasopressor agents before, during, and after the first three weeks of MAOI and TCA administration in dogs.

Cardiac myonecrosis in hypertensive crisis associated with monoamine oxidase inhibitor therapy

A young woman taking tranylcypromine for depression was hospitalized with severe chest pain and hypertension after eating cheese. Electrocardiography initially showed arrhythmias and precordial ST segment depression. Myocardial creatine kinase values were elevated, and echocardiography showed regional ventricular dysfunction, suggestive of focal cardiac myonecrosis. The cardiovascular pathophysiology of tyramine hypertensive crisis and related catecholamine excess states, including pheochromocytoma and clonidine withdrawal, is reviewed. Cardiac myonecrosis is a potential adverse effect of the hypertensive crisis associated with monoamine oxidase inhibitor use. Psychiatric indications for monoamine oxidase inhibitors may be expanding, but clinicians should continue to exercise caution in the use of these agents.

The use of monoamine oxidase inhibitors and tricyclic antidepressants in the treatment of migraine and mixed headaches

The use of monoamine oxidase inhibitors and tricyclic antidepressants in the treatment of migraine and mixed headaches

Fatal Malignant Hyperthermia as a Result of Ingestion of Tranylcypromine (Parnate®) Combined with White Wine and Cheese

Fatal malignant hyperthermia occurred in a patient who was taking tranylcypromine (Parnate) and ingested wine and cheese. The case findings are presented along with a review of the literature concerning adverse interactions between monoamine oxidase (MAO) inhibitors and certain foods and beverages. Hyperthermia and its possible causative mechanisms and treatments are discussed. The facts suggest that the complicated dietary restrictions attending the use of MAO inhibitors and the possibility of severe and even catastrophic reactions resulting from violations of these restrictions make the use of these drugs fraught with danger and therefore not a first choice for the treatment of depression.