Posted by AndrewB on November 22, 2000, at 4:22:33
I think it is clear, that for some, dopamine drugs can be of benefit. While not all psychiatrists will except such a notion, I have come to believe, as well as others at this site, that types of dopamine system hypofunction seem clearly to be involved with certain mood disorders (especially those with atypical depression) and is also the root of some types of social anxiety and anergia.
It can be speculated that there are different profiles of dopamine dysfunction. If this is true, this goes a long way towards explaining why some people respond to some dopaminergic drugs and not to others. Presumably the drugs that do work for a person, do so by correcting the dopaminergic hypofunction which is specific to their receptor profile.
For example, SSRIS, in one sense, can be considered dopaminergic drugs since the act to upregulate post-synaptic dopamine receptors. Interestingly, people who responded to SSRIS were found to have at the outset of treatment sub-functional post-synaptic receptors, while non-responders were found to have normal function at these receptors. One conclusion is that SSRIs are effective, and only effective, if a person has dopaminergic hypofunction at the post-synaptic receptors.
Pramipexole has been indicated to augment the effect of SSRIs, possibly indicating that pramipexole is able to upregulate post-synaptic receptors yet further.
Undeniably, some people respond well to Zyprexa, sulpiride or amisulpride. These are atypical antipsychotics whose action at low doses, biochemically, is the mirror image of their action at high doses. At low doses they have the potential to treat dopaminergic hypofunction via the pre-synaptic receptors. That is, they block the pre-synaptic receptor from uptaking dopamine and breaking it down, thus increasing dopamine in the synaptic cleft. (Note: amisulpride does not normally block D2/D3 post-synaptic receptors in low doses). It isn't clear, but a person who responds to pramipexole may not respond to one of these meds., possibly because they treat a different type of dopaminergic dysfunction in the receptor profile.
What does seem to be clear though is that a response to sulpiride does not guarantee a response to amisulpride or Zyprexa. It has been suggested that a person’s specific binding capacities at their receptor sites ( and the differential between the post and pre-synaptic receptor binding capacities) may determine which drug (each with its own binding potentials) is effective for the individual.
Selegiline and stimulants are two other dopaminergics where it is unclear who they will work for, and if they will work for some with dopaminergic hypofunction but not others.
The conception and understanding of dopaminergic disorders is in a state of evolution and hopefully the next five years or so made shed some light on protocols for administering dopaminergic drugs and in which way individuals vary in their type of dopaminergic dysfunction.
Until this day comes, it is a bit of hit and miss, trial and error as to finding if one has dopaminergic dysfunction and what medicines can best treat it.
My view, is that if a person has failed to respond to two or more SSRIs, and has symptoms such as anhedonia, anergia, social anxiety, emotional blunting, detachment, constant low mood or pessimism, and a lack of motivation (among other symptoms) - they should try dopaminergic drugs.
The question is what to try first. One strategy is to try a spectrum of dopaminergics in relatively rapid fashion, since their trial need not run as long as those with SSRIs and most other antiDs. For example, a 2 week trial with amisulpride or Zyprexa, a 10 day trial with 3 different stimulants and a 3 week trial with pramipexole. Also selegiline can be started concurrently with any of these trials, with an effect maybe not being seen for 30 or 45 days.
...........Some tips to remember:...............
Amisulpride and sulpiride work best when combined with an arousal agent (selegiline, a stimulant or adrafinil)
Zyprexa usually has more side effects than amisulpride, and while it has its place, for pure dopaminergic hypofunction it can be problematic.
Anxiety, which can occur with stimulants or selegiline, may be counteracted by a low dose antipsychotic.
Pramipexole can work well with SSRIs or bipolar meds. It also lowers prolactin, and like selegiline, has a longterm effect of preventing dopamine neuron die off, a natural consequence of aging. It can counter the sexual side effects of SSRIs and I speculate it can counteract the sexual side effects of antipsychotics. It has been noted to increase libido on its own.
JohnL has sugested remeron is a good adjunct to amisulpride if serotonin and NE imbalance are still an issue.
Zyprexa can be a good adjunct with bipolars and also with MAOIs and SSRIs. It is not clear if amisulpride may also be combined effectively in this way.
BTW: JohnL, pramipexole created no effect for me, positive or adverse, other than improving my physical coordination. Therefore I stopped it.
Best wishes,
AndrewB
poster:AndrewB
thread:49222
URL: http://www.dr-bob.org/babble/20001115/msgs/49222.html