Time to Reconsider Monoamine Oxidase Inhibitors for Obsessive Compulsive Disorder?: A Case Series Using Phenelzine.

PURPOSE/BACKGROUND: Despite the availability of a range of efficacious evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them in practice. Monoamine oxidase inhibitors (MAOIs) show efficacy in the treatment of depression and certain anxiety disorders (such as social anxiety disorder). METHODS/PROCEDURES: We survey the evidence base from case reports, and clinical trials, regarding use of MAOIs in OCD. We then present new data from a case series collected in routine clinical practice in a specialist clinical service. FINDINGS/RESULTS: In 9 treatment-resistant patients whose OCD had not improved with at least 2 standard treatment trials, 3 had marked clinical improvement (>35% improvement on YBOCS) on phenelzine, 3 had some improvement (15-34.9%), and 3 showed minimal or no improvement (<15%). In the 3 patients who experienced minimal/no improvement, 2 had discontinued early because of lack of tolerability, and the other patient discontinued after 4 weeks because of perceived lack of symptom benefit. IMPLICATIONS/CONCLUSIONS: We suggest that (1) MAOIs in treatment-resistant OCD require appropriate research scrutiny in large-scale randomized controlled trials; and (2) MAOIs merit consideration as a treatment option in individual cases of OCD, particularly in specialist settings where first-line interventions have proven inadequate to manage severe symptoms.

Phenelzine and Morphine Drug-Drug Interaction? A Literature Review.

The objectives of this manuscript are to describe a case report of a patient whose phenelzine maintenance therapy was discontinued due to concern for a phenelzine-morphine drug interaction, to review the available literature regarding the potential for this drug-drug interaction, and provide recommendations for this clinical scenario. A PubMed/MEDLINE literature search was conducted and all publications determined to be relevant to this case report were included. Literature describing in vitro data, case reports/human studies, and review articles concerning the interaction between morphine and monoamine oxidase inhibitors (MAOIs) were included. A total of 14 publications pertinent to the potential phenelzine-morphine interaction were included in this review including 5 in vitro studies, 4 human studies, and 6 review articles detailing the drug interaction profile between opioids and antidepressants. Of these publications, only a single case report of a potential drug interaction between morphine and phenelzine was identified. The literature suggesting a drug interaction between morphine and phenelzine is limited. The combination of phenelzine and morphine, with close monitoring for signs and symptoms of serotonin syndrome, is reasonable for patients with appropriate indications for both agents.

MAOIs - does the evidence warrant their resurrection?

OBJECTIVE: The place of monoamine oxidase inhibitors (MAOIs) in psychiatry is reviewed, and the question posed as to whether they are now justifiably disregarded by prescribers. METHOD: Multiple databases (PubMed, Medline, Embase, Cochrane) were interrogated to provide an overview regarding the use, efficacy and toxicity of MAOIs. Data regarding funded use of these agents in New Zealand were obtained from PHARMAC. RESULTS: Evidence supports the use of MAOIs in major depressive disorder, certain anxiety disorders and, to lesser extent, bipolar depression. Older non-selective agents, such as phenelzine and tranylcypromine, have distinctive efficacy in 'atypical' and treatment-resistant depression, but at the cost of serious tolerability problems. Their relegation and perception by clinicians as 'last resort' medications - if considered at all - has occurred in the context of various concerns, notably dietary restrictions, potential adverse drug interactions and the usual requirement for divided doses. CONCLUSIONS: Sufficient evidence supports consideration of MAOIs in treatment-refractory and atypical depressive disorders, and in social anxiety disorder. Psychiatrists in training need to gain experience in using these agents.

Serotonin syndrome probably triggered by a morphine-phenelzine interaction.

Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. Evidence supporting an association between nonserotonergic opiates, such as oxycodone or morphine, and serotonin syndrome is very limited and even contradictory. In this case report, we describe a patient who developed serotonergic-adverse effects likely precipitated by an interaction between morphine and phenelzine. A 57-year-old woman presented to the emergency department with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, confusion, sweating, tachycardia, and nausea over the previous week. On admission, her blood pressure was 185/65 mm Hg, and clonus was noted in the lower extremities. The patient was hospitalized 10 days earlier for cellulitis of the left breast secondary to a left mastectomy 5 months earlier, and a short course of oral morphine was prescribed for pain control. Her routine medications consisted of aspirin, atorvastatin, bisoprolol, clopidogrel, gabapentin, omeprazole, phenelzine, and ramipril. Supportive measures were initiated on admission. Phenelzine and morphine were discontinued immediately, leading to a progressive resolution of symptoms over the next 48 hours. Phenelzine was restarted on discharge without further complications. Use of the Drug Interaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of serotonin syndrome and the combination of morphine and phenelzine. The mechanism underlying this interaction, however, remains unclear and warrants further investigation. Clinicians should carefully weigh the risk and benefits of initiating morphine in patients taking monoamine oxidase inhibitors or any other serotonin-enhancing drugs.

The comprehensive management of pregnant women with major mood disorders: a case study involving phenelzine, lithium, and quetiapine.

Pregnancy in women with severe mental illness (SMI) often bring added dimensions of complexity; considering that this group of women are choosing to have children at increasing rates, more highly complex cases will require management. A 31-year-old primigravida with a diagnosis of bipolar affective disorder was treated with an antidepressant, mood stabiliser and antipsychotic. This case discusses preconception counselling, pregnancy and labour management that resulted in the delivery of a 4,200 g baby at 39 weeks by emergency caesarian section. This case highlights the collaborative approach to care that is needed in this group of women and the need for increasing awareness and knowledge in health professionals. It follows the management from preconception through to the postpartum period.

["Addiction" to phenelzine - case report]. / ,,Uzaleinienie" od fenelzyny - opis przypadku.

The use of non-selective monoamine oxidase inhibitors (IMAO) may be associated with the risk of addiction, which is confirmed by case studies published so far. Harmful use of antidepressants in patients with affective disorders and anxiety is not frequent, but due to the fact that in clinical practice can meet with this phenomenon, we present the case of a 30-year-old patient with a history of using phenelzine who presented a combination of symptoms that meet criteria for addiction. The current classification of ICD- 10 does not consist the diagnosis of dependence on antidepressants. In this case, the category F55.0: abuse of a substance which does not cause addiction, should be used. In the literature most often mentioned as a possible substances with addictive potential is a group of non-selective MAO, particularly tranylcypromine. The mechanism of non-selective MAO dependence may be associated with the similarity of their chemical structure to amphetamine (both amphetamine and IMAO are derivatives of phenylethylamine), although the mechanism of action is different. Furthermore, it was noted that there is a group of patients in whom treatment with IMAO is associated with greater risk of abuse of these substances. The study contains the characteristics of this group of patients.

Phenelzine-induced myocardial injury: a case report.

INTRODUCTION: Phenelzine is an irreversible monoamine oxidase inhibitor (MAOI). Hypertensive reactions after ingestion of tyramine-rich foods such as cheese are well known. However, a review of the available medical literature found no previous reports of myocardial infarction resulting from the ingestion of cheese by a patient taking a MAOI. CASE REPORT: A 34-year-old female taking phenelzine for depression developed severe chest pain 1 h after eating cheese. She was hypertensive and the electrocardiography showed ischemic changes in the antero-lateral chest leads. The chest pain and elevated blood pressure were relieved with intravenous morphine and nitroprusside. The initial serum troponin I level was normal, but serial repeat levels showed a rising trend with a peak at 4.89 ug/L (reference range <0.05 ug/L) 6 h after the initial blood draw, suggestive of a non-ST elevation myocardial infarction. The patient subsequently developed hypotension 4 h after another therapeutic dose of phenelzine was served to the patient 4 h after her admission to the ED. This was corrected with at least 2 L of intravenous normal saline boluses. Subsequent EKGs and Sestamibi scan showed no evidence of cardiac ischemia. She was discharged home after a hospital stay of 3 days. DISCUSSION: We believe this to be the first reported case of myocardial infarction resulting from ingestion of cheese in a patient taking a MAOI. It might be expected that hypertensive crisis could lead to a myocardial infarction, but a review of the medical literature found no such cases reported.

[Irreversible, non-selective monoamine oxidase inhibitors]. / Irreversible, uselektive monoaminoksidasehemmere.

Irreversible, non-selective monoamine oxidase (MAO) inhibitors were among the first antidepressants. No drugs in this group are currently marketed in Norway, but many physicians will see patients using them, as they can be prescribed on a named patient basis after application to the Norwegian Medicines Agency. This article presents adverse effects, interactions and precautions related to the use of these drugs.

Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial.

BACKGROUND: Up to a third of elderly patients with major depressive disorder do not respond to a first course of treatment with an antidepressant. There is a lack of controlled studies evaluating therapies for treatment-resistant depression in late-life depression, and no randomized controlled studies assessing the efficacy and tolerability of lithium augmentation in elderly patients have been published. METHOD: Twenty-nine elderly inpatients with major depressive disorder according to DSM-IV criteria who had previously failed to respond to 1 or more adequate trials with a tricyclic antidepressant or venlafaxine were included in a 6-week, open, randomized, controlled study with a 2-year follow-up. Subjects received either lithium augmentation or the monoamine oxidase inhibitor phenelzine. The primary outcome criterion was remission, defined as a final score of less than or equal to 10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Response was defined as at least 50% reduction on the MADRS or the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Twenty-eight subjects completed the trial. Remission on the MADRS was achieved by 33.3% of the lithium patients, compared with none of the phenelzine patients (p = .042). Response also showed a difference in favor of lithium augmentation (p = .035 on both the MADRS and the HAM-D). Overall tolerability was good, with no dropouts due to side effects. Subjective memory impairment was more prevalent among patients receiving phenelzine (p = .002), and tremors were significantly more prevalent among patients receiving lithium (p = .002). During the 2-year follow-up, 25 patients (86.2%) did achieve remission, particularly on prolonging the lithium treatment (5 patients) or on lithium augmentation to phenelzine (5 patients). CONCLUSION: Lithium was more effective than phenelzine in elderly patients with treatment-resistant major depressive disorder, while tolerance of both treatments was remarkably good in this group of elderly inpatients with many comorbid medical disorders. CLINICAL TRIALS REGISTRATION: Controlled-trials.com identifier is RCTN93105957.

Efficacy and safety of antidepressant monotherapy in the treatment of bipolar-II depression.

Sparse data exist regarding the risks and benefits of treating bipolar-II depression with antidepressants alone. On the basis of studies of bipolar-I patients, treatment guidelines suggest antidepressants should be augmented with mood stabilizers. Whether these recommendations apply to bipolar-II is unclear. A post-hoc analysis of a double-blind study, which compared the relative efficacy of placebo, imipramine and phenelzine in depressed outpatients. Patients rated 1 ('very much improved') or 2 ('much improved') on the Clinical Global Inventory Scale were considered responders. In an intent to treat analysis, no significant differences between bipolar patients (N=62) and unipolar patients (N=248) in response rates to placebo, imipramine and phenelzine were seen. No patient developed manic symptoms that required medication discontinuation or mood stabilizer augmentation. Antidepressant monotherapy was found to be a safe and effective treatment for bipolar-II depression.

Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs.

Serotonin syndrome is a potentially lethal adverse drug reaction that may occur in patients taking proserotoninergic medications. Drug interactions are often responsible for the causation of this syndrome. We report two cases of severe serotonin syndrome induced by the administration of cyclobenzaprine in postoperative patients already receiving another proserotoninergic drug (phenelzine in one case and duloxetine in the other). In both cases, symptoms of autonomic instability and severe agitation started within hours of initiation of cyclobenzaprine and fully resolved within 3 days after discontinuing the proserotoninergic drugs. We conclude that cyclobenzaprine should be used with extreme caution in patients receiving other serotonin-enhancing drugs; these patients should be closely monitored for manifestations of serotonin syndrome.

Quetiapine for insomnia associated with refractory depression exacerbated by phenelzine.

OBJECTIVE: To report the successful treatment of phenelzine-associated insomnia with low-dose quetiapine in a patient with refractory depression. CASE SUMMARY: A 42-year-old white man with severe major depression unresponsive to selective serotonin-reuptake inhibitors, bupropion, and tricyclic antidepressants improved following treatment with the monoamine oxidase inhibitor (MAOI) phenelzine. Insomnia, present to a moderate degree prior to antidepressant therapy, worsened markedly following phenelzine treatment and failed to respond to diphenhydramine, temazepam, triazolam, clonazepam, zolpidem, or trazodone given at high therapeutic doses. Sleep disturbance resolved with low-dose (50 mg) adjunctive quetiapine, with no adverse effects. DISCUSSION: Major depression refractory to standard therapy is a common and serious condition. Some cases respond to MAOIs; however, orthostatic hypotension and insomnia frequently occur. Potentially serious MAOI interactions with psychotropic drugs have raised concerns about combining these agents. In this case, a failure of a number of other medications known to treat MAOI-associated insomnia safely prompted a trial of quetiapine. Despite the possibility that enhanced serotonergic activity might have resulted in serotonin syndrome, no adverse interactions between phenelzine and quetiapine were noted. The use of low-dose, once-daily quetiapine, along with its unique binding properties, may account for its increased safety in combination with phenelzine. CONCLUSIONS: This case illustrates that low-dose quetiapine may be an alternative treatment for phenelzine-associated insomnia. Further case reports are needed to establish the safety and effectiveness of combining these agents.