Moclobemide
Encyclopedia
Moclobemide is a monoamine oxidase inhibitor
(MAOI) drug primarily used to treat depression
and social anxiety
. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company.
(RIMA), a type of monoamine oxidase inhibitor (MAOI), and acts on serotonin
, norepinephrine
(noradrenaline), and dopamine
. Moclobemide suppresses the unstimulated release of certain proinflammatory cytokine
s which are believed to be involved in the pathophysiology of major depression and stimulates the release of anti-inflammatory cytokines. The MAO inhibition of moclobemide wears off within 24 hours. Moclobemide is chemically unrelated to irrversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine
. Moclobemide produces several active metabolite
s that are weaker at inhibiting MAO-A than the parent compound; at least one active metabolite is a potent inhibitor of MAO-B, but due to the very low levels of the MAO-B inhibiting active metabolite that occurs in humans moclobemide is considered to be a selective MAO-A inhibitor.
Depressed people show improved sleep, with an increase in stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. A small study found the oppsite happens in healthy men, a slight suppression of REM occurs; also it was found that cortisol
levels may be elevated by moclobemide. Moclobemide also has neuroprotective properties in it's demonstrated anti-hypoxia
effects. Additionally moclobemide has cognitive enhancing properties.
Platelet MAO levels are not significantly affected by moclobemide, possibly because it is a reversible MAOI. A single 300 mg dose of moclobemide inhibits 80% of monoamine oxidase
A (MAO-A) and 30% of monoamine oxidase B (MAO-B), blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake
inhibition of any of the neurotransmitter
s occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria
, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier than typically noted with TCAs/SSRIs).
Moclobemide should not generally be taken concurrently with other antidepressants, because of the likelihood of significant drug interactions. Some very specific regimens may combine moclobemide with a tricyclic or SSRI antidepressant. A washout period of two days is necessary when switching to a tricyclic antidepressant, and for SSRIs, a washout period of at least four to five half-lives is required.
, CYP2D6
and CYP1A2
. Less than 1 percent of the drug is excreted unchanged; 92 percent of the metabolised drug is excreted within the first 12 hours. The main metabolites are the N-oxide Ro 12-5637 and lactam derivative Ro 12-8095; active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine). The main degradation pathway of moclobemide is oxidation. About 44 percent of the drug is lost due to the first pass effect
through the liver. Age and renal status do not affect the pharmacokinetics of moclobemide; however impaired hepatic function slows down the elimination of moclobemide.
Steady state concentrations are established after one week of three times daily dosing. It has been suggested that changes in dose should not be made with a gap of no less than a week. Moclobemide has good pentration across the blood brain barrier with peak plasma levels within the central nervous system occuring 2 hours after administration.
Similar to other MAOI's, reversible MAOI's such as moclobemide may also be effective in a range of other psychiatric disorders.
In efficacy studies for the treatment of major depressive disorder, moclobemide has been found to be significantly more effective than placebo, as effective as the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), and somewhat less effective than the older, irreversible MAOIs phenelzine
and tranylcypromine
. In terms of tolerability, however, moclobemide was found to be comparable to the SSRIs and better tolerated than the TCAs and older MAOIs. A 52 week followup of 102 people on moclobemide found that the therapeutic effects were retained with long-term use as well as safe and well tolerated.
Caution:
Individuals who have liver impairment may require dose reduction of about one half or one third.
side effects which are low with moclobemide; cardiovascular adverse effects are also lower with moclobemide compared to tricyclic antidepressants. Adverse effects on cognition, which are a particular concern in the elderly, are minimal and, in fact, evidence suggests that moclobemide may actually enhance cognition, especially memory. Compared to trazadone there is significantly less of an impairment on vigilance. Research has found evidence that moclobemide may be able to counter cholinergic induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia. Liver toxicity does not occur with moclobemide. Moclobemide has a similar efficacy profile compared to other antidepressants but is very significantly superior in terms of tolerance and safety profile. Moclobemide has little effect on psychomotor
functions. Other side effects include, restlessness, paraesthesias, nausea and sleep disturbances such as difficulty falling asleep.
Moclobemide is relatively well-tolerated. Severe side effects are infrequent. The side effect profile is as follows:
treatment with benzodiazepines or neuroleptics during the initial phase of treatment. It can be advisable to hospitalize such patients until remission is stable.
however, causes a significant rise in moclobemide levels and therefore if the combination is used, lower doses of moclobemide have been recommended. There is little increase in the effects of alcohol when combined with moclobemide and, in fact, moclobemide causes a reduction in alcohol related impairments.
by moclobemide is only one seventh to one tenth of that of irreversible MAOIs. Nevertheless, the patient should avoid excessive consumption of foods containing tyramine
(e.g. cheddar cheese, fava beans, chianti wine) in order to avoid a rise in blood pressure.
Patients with significantly reduced liver function should receive 1/3 to 1/2 of the normal dose.
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI) drug primarily used to treat depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and social anxiety
Social anxiety
Social anxiety is anxiety about social situations, interactions with others, and being evaluated or scrutinized by other people...
. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company.
Pharmacology
Moclobemide is a reversible inhibitor of monoamine oxidase AReversible inhibitor of monoamine oxidase A
Reversible inhibitors of monoamine oxidase A are a class of drugs which selectively and reversibly inhibit the enzyme monoamine oxidase A . They are used clinically in the treatment of depression and dysthymia, though they have not gained widespread market share due to limited efficacy relative to...
(RIMA), a type of monoamine oxidase inhibitor (MAOI), and acts on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline), and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
. Moclobemide suppresses the unstimulated release of certain proinflammatory cytokine
Proinflammatory cytokine
A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Examples include IL-1 and TNF alpha....
s which are believed to be involved in the pathophysiology of major depression and stimulates the release of anti-inflammatory cytokines. The MAO inhibition of moclobemide wears off within 24 hours. Moclobemide is chemically unrelated to irrversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
. Moclobemide produces several active metabolite
Active metabolite
- Prodrugs :Sometimes drugs are formulated deliberately so they will break down inside the body to form the active drug, these are called prodrugs. The reason for this may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better...
s that are weaker at inhibiting MAO-A than the parent compound; at least one active metabolite is a potent inhibitor of MAO-B, but due to the very low levels of the MAO-B inhibiting active metabolite that occurs in humans moclobemide is considered to be a selective MAO-A inhibitor.
Depressed people show improved sleep, with an increase in stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. A small study found the oppsite happens in healthy men, a slight suppression of REM occurs; also it was found that cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
levels may be elevated by moclobemide. Moclobemide also has neuroprotective properties in it's demonstrated anti-hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
effects. Additionally moclobemide has cognitive enhancing properties.
Platelet MAO levels are not significantly affected by moclobemide, possibly because it is a reversible MAOI. A single 300 mg dose of moclobemide inhibits 80% of monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
A (MAO-A) and 30% of monoamine oxidase B (MAO-B), blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
inhibition of any of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier than typically noted with TCAs/SSRIs).
Moclobemide should not generally be taken concurrently with other antidepressants, because of the likelihood of significant drug interactions. Some very specific regimens may combine moclobemide with a tricyclic or SSRI antidepressant. A washout period of two days is necessary when switching to a tricyclic antidepressant, and for SSRIs, a washout period of at least four to five half-lives is required.
Pharmacokinetics
Moclobemide is rapidly absorbed. Peak plasma levels occur 0.3 to 2 hours after oral administration. The bioavailability increases during the first week of therapy from 60% to 80% and more. The elimination half-life is 1 to 2 hours. Despite its short half-life the pharmacodynamic action of a single dose persists for approximately 16 hours. The drug is almost completely metabolized in the liver by 3 enzymes, CYP2C19CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...
, CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
and CYP1A2
CYP1A2
Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body...
. Less than 1 percent of the drug is excreted unchanged; 92 percent of the metabolised drug is excreted within the first 12 hours. The main metabolites are the N-oxide Ro 12-5637 and lactam derivative Ro 12-8095; active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine). The main degradation pathway of moclobemide is oxidation. About 44 percent of the drug is lost due to the first pass effect
First pass effect
The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
through the liver. Age and renal status do not affect the pharmacokinetics of moclobemide; however impaired hepatic function slows down the elimination of moclobemide.
Steady state concentrations are established after one week of three times daily dosing. It has been suggested that changes in dose should not be made with a gap of no less than a week. Moclobemide has good pentration across the blood brain barrier with peak plasma levels within the central nervous system occuring 2 hours after administration.
Animal toxicology
- Acute toxicity: The oral values in mouse and rat are quite high, indicating a wide therapeutic indexTherapeutic indexThe therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....
. LD50 for mice is 730 mg/kg and for rats 1,300 mg/kg. In dogs doses in excess of 300 mg/kg led to vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, salivation, ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, and drowsiness. - Chronic toxicity: In an 18-months-study in rats with 10 mg/kg no signs of chronic toxicity were noted, with 50 mg/kg and 250 mg/kg only a slight loss of weight, and with 250 mg/kg mildly elevated Alkaline phosphataseAlkaline phosphataseAlkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
and Gamma-GT. Studies in dogs revealed no toxicity relevant for humans. No evidence for a possible hepatic or cardiovascular toxicity was found.
Uses
- DepressionClinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
; most experience exists with major depression according to DSM-III, with both endogenous and non-endogenous depression responding; in addition moclobemide has a fast onset of action compared to other antidepressants and is significantly more tolerable than the tricyclic antidepressants. Due to its superior safety profile, moclobemide has been recommended as a first line agent for the treatment of depression in the elderly.
Similar to other MAOI's, reversible MAOI's such as moclobemide may also be effective in a range of other psychiatric disorders.
In efficacy studies for the treatment of major depressive disorder, moclobemide has been found to be significantly more effective than placebo, as effective as the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), and somewhat less effective than the older, irreversible MAOIs phenelzine
Phenelzine
Phenelzine is a non-selective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic...
and tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...
. In terms of tolerability, however, moclobemide was found to be comparable to the SSRIs and better tolerated than the TCAs and older MAOIs. A 52 week followup of 102 people on moclobemide found that the therapeutic effects were retained with long-term use as well as safe and well tolerated.
Contraindications and cautions
Contraindications:- Hypersensitivity to moclobemide
- States of severe confusion
- Concomitant treatment with selegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
- Concomitant treatment with clomipramineClomipramineClomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...
- Concomitant treatment with SSRIs. After termination of SSRI treatment, moclobemide should not be used until four to five half-lives of the SSRI have elapsed (five weeks in the case of fluoxetineFluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
and two weeks otherwise). - Combination treatment with pethidinePethidinePethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
(Interaction may be fatal) - Combination treatment with dextromethorphanDextromethorphanDextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
- Pediatric patients (no sufficient data exists)
Caution:
Individuals who have liver impairment may require dose reduction of about one half or one third.
- Patients with schizophrenia (psychosis may exacerbate, longterm treatment with neuroleptics should be continued.)
- Patients with hyperthyroidismHyperthyroidismHyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
(overfunction of the thyroid gland) and phaeochromocytoma. Hypertensive reactions are possible, therefore treatment with moclobemide cannot be recommended. - Patients with uncontrolled hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
- Patients with bipolar disorderBipolar disorderBipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
.
Pregnancy and lactation
The doses of moclobemide are very low and therefore it has been concluded that moclobemide is unlikely to have any adverse affect on a suckling baby.Side effects
Side effects with moclobemide are minimal and mostly consist of some nausea and dizziness in a small number of people at the start of therapy. The tolerability of moclobemide is similar in woman and men and it is also well tolerated in the elderly. Moclobemide has been found to be superior to tricyclic antidepressants in terms of side effects, especially anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
side effects which are low with moclobemide; cardiovascular adverse effects are also lower with moclobemide compared to tricyclic antidepressants. Adverse effects on cognition, which are a particular concern in the elderly, are minimal and, in fact, evidence suggests that moclobemide may actually enhance cognition, especially memory. Compared to trazadone there is significantly less of an impairment on vigilance. Research has found evidence that moclobemide may be able to counter cholinergic induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia. Liver toxicity does not occur with moclobemide. Moclobemide has a similar efficacy profile compared to other antidepressants but is very significantly superior in terms of tolerance and safety profile. Moclobemide has little effect on psychomotor
Psychomotor
Psychomotor can refer to:* Psychomotor learning* Psychomotor retardation* Psychomotor agitation...
functions. Other side effects include, restlessness, paraesthesias, nausea and sleep disturbances such as difficulty falling asleep.
Moclobemide is relatively well-tolerated. Severe side effects are infrequent. The side effect profile is as follows:
- Blood and blood-forming-organs: Isolated cases of bone-marrow-damage.
- Allergic Reactions/Hypersensitivity: Occasionally isolated urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
without other symptoms, isolated cases of anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
involving urticaria, angioedemaAngioedemaAngioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...
, asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, and rapid fall in blood pressure. - Psychiatric Reactions: Occasionally insomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
and agitationPsychomotor agitationPsychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
, increased anxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
; infrequent are confusionConFusionConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
(readily reversible after termination of treatment) and nervousnessAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
. Preexisting schizophrenia may exacerbate under moclobemide therapy (see under Cautions). - Central and Peripheral Nervous System: Occasionally headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, and vertigoVertigo (medical)Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
, infrequent peripheral neuropathy, rarely seizures. Moclobemide may impair the capability of the patient to drive or operate machinery, because it can cause vertigo, headache or rarely seizures. - Eyes: Infrequent is blurred vision.
- Cardiovascular: Changes in blood pressure (hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
) are infrequent. - Gastro-Intestinal Tract: NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and dry mouth, infrequently stomach upset, heartburnHeartburnHeartburn, also known as pyrosis or acid indigestion is a burning sensation in the chest, just behind the breastbone or in the epigastrium...
, diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, and obstipation. - Skin: Occasionally rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, pruritus and redness of skin. - Breast: Rarely breast enlargement and secretion of milk in both sexes (due to elevated prolactinProlactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
levels).
Agitated patients or patients with suicidal thoughts
Moclobemide has no sedative properties. Therefore, agitated patients or those with suicidal thoughts should receive sedative/anxiolyticAnxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
treatment with benzodiazepines or neuroleptics during the initial phase of treatment. It can be advisable to hospitalize such patients until remission is stable.
Interactions
Moclobemide has less interactions than the irreversible MAOI's. CimetidineCimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
however, causes a significant rise in moclobemide levels and therefore if the combination is used, lower doses of moclobemide have been recommended. There is little increase in the effects of alcohol when combined with moclobemide and, in fact, moclobemide causes a reduction in alcohol related impairments.
- Other MAO-Inhibitors, SSRIs, SNRISNRISNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...
s, clomipramineClomipramineClomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...
, selegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
, pethidine/meperidinePethidinePethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
, dextromethorphanDextromethorphanDextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
, tramadolTramadolTramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
and MDMA: Development of serotonin syndromeSerotonin syndromeSerotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
, which may be fatal, is possible. MAOIs, in general, interfere with the metabolism of SSRIs. - OpiateOpiateIn medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
s: Moclobemide potentiates the analgesic action of opiates. - Sympathomimetics: Risk of serious hypertensive crisis. Combination therapy is not recommended.
- CimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
: Metabolization of moclobemide is reduced; dosage of moclobemide should be reduced to 1/3 to 1/2 of the normal dose. - Antidepressants without serotonergic action: Moclobemide treatment is possible after a latent period of 48 hours. The moclobemide dose should not exceed 300 mg daily during the first week.
- BenzodiazepineBenzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s: Moclobemide doubles the half-life of diazepam and the active metabolite nordiazepam. The diazepam dose should be reduced accordingly.
Dietary advice
Irreversible MAOI's can cause unpleasant and occasionally dangerous side effects such as a hypertensive crises after intake of food or drink containing indirectly-acting sympathomimetic amines such as tyramine. This is sometimes referred to as the 'cheese effect'. These side effects are due to irreversible inhibition of MAO in the gut and vasomotor neurones. However, the reversible MAOI antidepressants such as mocobemide have a much different side effect profile in this regard. Of 2300 people in multiple clinical trials who were treated with moclobemide in doses up to 600 mg with no dietry restrictions, none experienced a tyramine-mediated hypertensive reaction. As the pressor effect of moclobemide is so low, a strict diet is not necessary, in contrast to irreversible MAOIs. However, some rare cheeses that have a high tyramine level may possibly cause a pressor effect and require caution. No significant rise in blood pressure occurs when moclobemide is combined with tyramine containing foods unlike irreversible MAOI's which cause a severe rise in blood pressure. The potentiation of the pressor effect of tyramineTyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
by moclobemide is only one seventh to one tenth of that of irreversible MAOIs. Nevertheless, the patient should avoid excessive consumption of foods containing tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
(e.g. cheddar cheese, fava beans, chianti wine) in order to avoid a rise in blood pressure.
Dosage
- Depression: The initial dose is 300 mg daily in 2 or 3 divided doses. In cases of severe or resistant depression the dose can be increased to 600 mg daily. One week should elapse before the dose is escalated, because bioavailability increases during the first week. The treatment should be continued for 4 to 6 weeks, before a determination regarding the success of moclobemide treatment is made.
- Social anxiety disorder: The recommended dose is 600 mg daily in 2 or 3 divided doses. Treatment is usually started with 300 mg daily on the first 3 days. The treatment should be continued for at least 3 to 4 weeks, before the therapeutic gain is determined. Physician and patient should be aware that the therapeutic prospects of moclobemide treatment in patients with chronic alcoholism are bad. As social phobia is a chronic disease, it can be advisable to treat patients on a long-term basis. In clinical studies moclobemide proved to be an efficient drug for maintenance.
Dosage in patients with liver or renal disease
Impairment of renal function does not alter metabolization or elimination of the drug. The dose does not need to be reduced.Patients with significantly reduced liver function should receive 1/3 to 1/2 of the normal dose.
Overdose
Intoxications with moclobemide as single agent are usually mild with reversible CNS disturbances and irritations of the GI tract. Patients with mixed intoxications (e.g. with other CNS active drugs) may show severe or life-threatening symptoms and should be hospitalized. Treatment is largely symptomatic and should be aimed at maintenance of the vital functions.History
The discovery of moclobemide as an antidepressant came about after it was initially investigated as a possible lipid lowering drug. Subsequent research found that moclobemide was far superior to tricyclic antidepressants in terms of side effects, being well tolerated in elderly patients.Further reading
- Scientific Information on Aurorix (German)
- PubChem Substance Summary: Moclobemide National Center for Biotechnology Information.