Posted by CaptainAmerica1967 on January 12, 2009, at 18:52:15
In reply to Re: MAOI TX in Severe+Resistant Depression » CaptainAmerica1967, posted by JadeKelly on January 12, 2009, at 16:34:33
I would expect that 15mgs of Ritalin would be safe as it's not much different than 10mgs.
Here's another aritcle from PsychTropical Research that says there's never been a death using MAOIs and Ritalin together as Ritalin really doesn't have any serotonin effects just noradrenaline.
http://www.psychotropical.com/CNS_stimulants_with_MAOIs.shtmlMethylphenidate and MAOIs have been in use together for 40 years, so it would be surprising if someone had not ingested the combination by now: death, or morbidity, from such an event has not been reported (whereas it has with amphetamine). Methylphenidate is most widely used as a treatment for attention-deficit hyperactivity disorder (ADH) in children. It has been supposed to have serotonergic effects; if that is so it would be predicted to be at high risk of precipitating serotonin toxicity if combined with MAOIs. There are no definite case reports indicating serotonin toxicity with methylphenidate in combination with MAOIs, or other serotonergic drugs (see above) [17-20].
Also, as with mirtazapine and amitriptyline, methylphenidate does not produce serotonergic side effects, or signs of serotonergic toxicity in over-dose or if combined with MAOIs (see Markowitz). Eg the Sherman case was not serotonin toxicity, but blood pressure elevation [21-28].
These observations of serotonergic side effects, and signs of serotonergic toxicity in over-dose, or if combined with MAOIs, have been proposed as a measure of a drugs clinically significant serotonergic effect in humans. If these effects are not produced clinically significant serotonergic effects are unlikely. [29-32].
Methylphenidate also appears safe in combination with MAOIs; see Feinbergs recent and helpful review of MAOIs and CNS stimulants.[1-33-35].
This is in keeping with its negligible 5-HT transporter affinity (>10,000 nmol) and apparent inability to raise brain serotonin levels. Unfortunately Rothmans data does not include methylphenidate so there is no releaser potency data. If methylphenidate acts as a releaser in humans then it would be predicted that its effect would be lessened by selective serotonin reuptake inhibitors (SSRIs)s [21-23-36].
Amphetamine
Amphetamine and MAOIs have also been in use together for 40 years and there are few deaths from apparent serotonin toxicity reported with amphetamine. Amphetamine has weak serotonergic effects; and there seems little risk of precipitating serotonin toxicity if combined with MAOIs. All the case reports with MAOIs and Amphetamine were prior to 1969. The only fatalities have been with MAOIs [37-44].
Amphetamine itself does not seem to produce typical serotonergic side effects, or signs of serotonergic toxicity in over-dose, except hyperreflexia, hyperkinesia (agitation) and hyperpyrexia. Deaths from hyperpyrexia and other causes, but without classic features of serotonin toxicity, have been described. [45-46].
Amphetamine may not be safe in combination with MAOIs (see Feinbergs and Markowitzs recent and helpful reviews of MAOIs and CNS stimulants). It seems to produce noradrenergic toxicity; presumably in the same way as tyramine does, by acting as a releaser. None of these cases were reported to exhibit features that would suggest serotonin toxicity. Several of these cases were fatalities (2 of these below are not cited in the Markowitz paper) [38-41-44].
However, chlorpromazine appears to ameliorate the toxicity symptoms with amphetamine / MAOI as it does with serotonin toxicity.[47].
Amphetamine is 50-100 times less potent for serotonin, both as a releaser and reuptake inhibitor, than for dopamine or noradrenaline (see table). Its 5-HT transporter affinity (~3800 nmol) is extremely weak. However, unlike methylphenidate there is animal work indicating amphetamine does increase serotonin levels [9-22].
In summary, amphetamine definitely has been involved in deaths with MAOIs, and exhibits significant toxicity with venlafaxine (probably serotonin toxicity, as opposed to noradrenergic toxicity). To what degree the toxicity with MAOIs is serotonergic remains uncertain, but most fatalities have been from intra-cerebral bleeding, not serotonin toxicity [2].
If CNS stimulants are to be used to augment monoamine oxidase inhibitors methylphenidate is probably safe; amphetamine is more risky, and can produce moderate noradrenergic toxicity, even at therapeutic doses and perhaps serotonergic side effects, and even serotonin toxicity in over-dose.
MDMA (Ecstasy) 3,4-methylenedioxymethamphetamine
Ecstasy is the street name for 3,4-methylenedioxymethamphetamine (MDMA). Large doses of MDMA cause a rapid release of endogenous serotonin from the stores in the presynaptic nerves; so much so that a substantial MDMA dose will deplete about eighty percent of the serotonin stores. The "half life" of endogenous serotonin is short and the usual duration of symptoms does not frequently allow the development of hyperthermia, although this is influenced by ambient temperature and physical activity.[48-49]
MDMA will occasionally produce, among other things, a picture which is essentially that of serotonin toxicity; however serotonin toxicity sufficiently severe to cause death with MDMA alone is rare.
However such reports as do exist conform with predictions from the spectrum concept of serotonin toxicity and the data in Rothman (see table). No cases of serotonin toxicity with MAOIs had been reported in the literature till 2003. There have been one or two cases where people taking moclobemide, presumably to enhance effects, have been too successful and have experienced severe reactions. I know of one death (unpublished) seemingly from cerebral infarction secondary to arterial spasm. The Vuori report is of four deaths, probably from serotonin toxicity [50].
poster:CaptainAmerica1967
thread:873284
URL: http://www.dr-bob.org/babble/20090104/msgs/873590.html