Sunday, March 21, 2010

Methadone and Psychiatric Medication Interactions

Methadone as discussed here is related to 'methadone maintenance treatment' for substance, usually heroin or opiate, addiction. Methodone can be used for pain management but there the further confounding factor of what the primary pain inducing illness make that a potentially very different discussion.

Because methadone has a long half life (length of time it takes for half the methadone to be metabolize) it's breakdown can be affected by other medications which are metabolized at the p4Because methadone has a long half life (length of time it takes for half the methadone to be metabolize) it's breakdown can be affected by other medications which are metabolized at the p450 site. Medications can 'compete' for this site and slow down the metabolism increasing the risk of overdose and respiratory failure. Methadone can further prolong the QT interval and cause cardiac arrhythmias.

Contraindications and cautions regarding concommittant drug use are not wholly inflexible rules but advise clinicians to be very aware of the risk benefit ratio and to consider alternative medications where possible. In methadone maintenance however it's always a "risky" business because the person for whom treatment is being initiated is already using dangerous street drugs of highly questionable origin and dosage. In addition they are not uncommonly using street clinics, sharing prescriptions and despite best intentions not necessarily being totally honest with the addiction doctor. Further, when a medication is listed under 'contraindications or cautions' it may be related to the dosages of medication used. A medication safe at lower dose in combination with another low dose medication may be associated with increased risk at increasing dosage.

Those psychiatric drugs which are contraindicated in combination with methadone are as follows:

  1. Ziprasidone – zeldox – can cause constipation/paralytic ileus, CNS depression, psychomotor impairment and QT prolongation,and cardiac arrythmias
  2. Phenothiazines – antipsychotics – thoridazine, fluphenazine, perphenazine, chlorpromazine, - can cause constipation/paralytic ileus, CNS depression, prolongation of QT interval, and cardiac arrhythmias. Here the consideration is most concerning if a methadone patient were given a long acting depot injection such as 'modecate'. The phenothiazines are not as commonly used to day but loxapine is and it's closely related to thorazine and chlorpromazine.
  3. Pimozide – antipsychotic – may cause cardiac arrhythmias – this is not a commonly used antipsychotic. It still has a special place for 'monosymptomatic delusional disorder' and has been used most recently when other antipsychotics have not been effective.
  4. MAOI's – atypical antidepressants – may increase risk of serotonin syndrome. These are rarely used these days and usually only after other antidepressant medications have been tried. It would be unlikely for a methadone patient to be started on an MAOI but it is possible for a person on MAOI's to seek methadone treatment.


    Caution should be used with these psychiatric medications:


    Buprenorphine – naloxone – revia – it may precipitate withdrawal in opioid-dependent persons increasing the risk of CNS depression and psychomotor depression. Naloxone is used as an opiod antagonist in the emergency but emergency doctors are well versed in the various scenarios where this might be problematic and the emergency is equipped to handle the consequences. The only community based place where this might arise is the use of Naloxone for treatment of Alcohol or Cocaine dependence.


    Clozapine – this is an atypical antipsychotic - it may increased the risk of paralytic ileus, CNS depression, QT prolongation, cardiac arrhythmia and hypotension. It's not unlikely that a person using clozapine might seek methadone treatment, however clozapine treatment is most often closely monitored and the patients on clozapine are mostly managed by teams with greater likelihood of awareness and prevention.


    Haloperidol – antipsychotic – commonly used especially in psychiatric emergencies – orally and IM routes of administration – it may increase risk of severe constipation/paralytic ileus, CNS depression, psychomotor impairment, hypotension, QT prolongation, and cardiac arrhythmias.


    Quetiapine – a commonly used antipsychotic , also used at low dose for sleep, became increasingly popular because it is one of least likely to cause tardive dyskinesia. It may increase risk of QT prolongation, cardiac arrhythmias, hypotension, CNS depression and psychomotor impairment. This is dosage related.


    Tricyclic antidepressants – these were the most commonly used antidepressants before the advent of the SSRI's, ie Prozac. The most commonly used are amitriptylline, desipramine and clomipramine. They've had a resurgence as a number of patients aren't responsive to the newer antidepressants and the tricyclics have shown benefit in pain disorders and depressions with psychosomatic aspects. The combination can cause severe constipation/paralytic ileus, CNS depression, psychomotorc impairment, hypotension, QT prolongation, and cardiac arrhythmias. This occurs as a result of additive effects.


    Venlafaxine – effexor – this is a very popular effective broad spectrum antidepressant which has been called 'side effexor' only because of it's tendency to have increasing side effects at higher dosage. It's use in combination with methadone can due to additive effects increase the risk for QT prolongation, cardiac arrhythmias, serotonin syndrome, and neuroleptic malignant syndrome.


    Other psychiatric medications which should be monitored include:


    Carbamezapine – this is an anti seizure medication which has been used for manic depressive disorder, bipolar mood disorders, impulse dyscontrol syndromes and for violence. It is the drug of choice for rage attacks especially those triggered by alcohol. It can decrease methadone levels and precipitate opioid withdrawal symptons.


    St. John's Wart – this is an effective antidepressant that has been demonstrated in evidence based studies in Europe. It's available here from over the counter health food stores with questionable dosage and quality of preparation. It is however used commonly in winter months here as an adjunctive treatment or alternative treatment and for those who are more sensitive to seasonal affective disorder. It may decrease methadone levels and precipitate opioid withdrawal because it induces hepatic metabolism.


    Acetominophen – Tylenol – pain killer – may increase risk of CNS and respiratory depression, profound sedation, and hypotension. Problems are a result of the additive effects and dosage related.


    Anticholinergics—atropine, benztropine, scopolamine - these can be used in parkinson's disorder and in combinations with antipsychotics to treat the side effects of antipsychotics. They may increase risk of severe constipation/paralytic ileus and other anticholinergic adverse effects as a result of the additive impact.


    Antihistamines – used for allergies, over the counter, and sometimes used for sleep – combination with methadone can increase constipation/ CNS depression, and psychomotor impairment – dose related additive effects.


    Benzodiazepines – ativan, clonazepam, diazepam, valium – may cause vasodilatation, severe hypotension, CNS and respiratory depression, psychomotor impairment – additive, dosage related response in combination with methadone.


    Cannabinoids – pot, hash, marijuana –also medicinal dronabinol - when combined with methadone can increase risk of CNS depression, psychomotor impairment , dosage related and additive


    Ethanol – alcohol – may increase risk of CNS and respiratory depression, and psychomotor impairment, effect is dosage related.

Citalopram – commonly used and relatively safe SSRI – may increase risk of serotonin syndrome.

Fluoxetine – Prozac – commonly used antidepressant - may increase methadone levels and increase risk of QT prolongation, cardiac arrhythmias, serotonin syndrome, and neuroleptic malignant syndrome.

Ginseng – may increase risk of sedation – additive

Loxapine – may increase risk of severe constipation/paralytic ileus, CNS depression, hypotension, and psychomotor impairment – additive effects

Mirtazepaine – may increase risk of CNS depression and psychomotor impairment.

Olanzepine – zyprexia – may increase riks of severe constipation/paralytic ileus, CNS depression, psychomotor impairment, hypotension – additive effects.

Paroxetine – paxil – may increase risk of serotonin syndrome and neuroleptic malignant syndrome

Pregabulin – used for pain disorders - may increase risk of CNS depression – additive effects

Rispiridone – very commonly used atypical antipsychotic – may increase risk of CNS depression, and hypotension

Sertraline – antidepressant – may increase risk of serotonin syndrome and neuroleptic malignant syndrome – additive effects

Trazadone –antidepressants and also used as sleep aid - may increase risk of CNS depression, psychomotor impairment, - additive effects

Valerian – used as an anti anxiety tea – risk of CNS depressants - has additive effects.

Valproic Acid –Divalproex – increased risk of CNS depression and psychomotor impairment.- additive effects.


These are just the psychiatric medications interactions known to date and he cautions associated. Mostly the effects are dosage related.

There are countless other medications that have be be monitored carefully espec ially in the antibiotic and cardiac and respiratory medications.

As some drug user 'sample' the drug cabinets of places they visit without consideration of the dire consequences that might occur the initial phase of methadone maintenance therapy is one of potential high benefit combined with increased risk. Patients often want dosage increases to be rapid but the standard recommendation is to start methadone at 20 mg daily witnessed use then increase by 5 and at most 10 mg a day. This allows for increased safety during the period of stabilization. It 's also a time of education and a time when clinicians and patients get to know each other and establish a therapeutic relationship with the inherent trust and increased disclosure and cooperation associated.

2 comments:

spiro malamas said...

Thank you for this vital info! I have herniated discs in my neck, and i am on methadone maintainance for pain management. I dont have an issue with street drugs, but i am into health and weight training; the problem i kept on taking, until today, a multivitamin with ginseng and other potent 'male power' herbs included in the formula! Needless to say, i kept on feeling like i couldnt breathe, and i almost passed out today!! I got pretty scared, so i went online, and found your awesome article!! Thank you!!

ILovePancakes said...

Just an fyi, the term "methadone maintenance" refers SPECIFICALLY, and ONLY to those taking methadone for drug addiction/dependence. While you are "maintaining" levels of methadone in your body for pain management, its not the same thing at all.
Also, you likely take small methadone doses in pill form. 10mg, 30mg, etc. Methadone Maintenance Therapy (MMT) is typically at 70-100mg daily, in liquid form, and is administered daily at a clinic or pharmacy.

This information is not for those on methadone for pain management, although there is obviously overlap.