NOTE: this is a commentary on some available psychopharmacological options especially with regard to depression. It is hardly an appropriate response to the threadstarter, who may only need to quit Paxil in order to regain his energy and clear his brain fog. Rather, this is in response to those posts basically amounting to "antidepressants are useless and/or unnecessary" and focusses on shedding light onto drugs that are unlikely to be considered as first-line treatments for depression. I might add that I tried paroxetine (Paxil or Seroxat) myself many years ago and to this day it remains the most amotivational, passivising substance I've ever experienced, and I've tried a lot. The worst periods of depression made me spend almost 70% of the time in bed, but paroxetine caused me to only get out of the bed to eat, and that was at a time that I was in a considerably better shape.
Chronic depressive states don't resolve on their own, so some kind of treatment is necessary in order to avoid a lifetime of misery or a premature death by suicide. Considering the risks of electroconvulsive treatment or psychosurgery, medication would seem the treatment of choice. Medications are not limited to mass-market pharmaceutical products, but may include anything from herbs to classic street drugs and research chemicals.
Serotonin reuptake inhibitors do appear to work for some people, especially those who have a problem with emotional stability or persistent negative emotions. On the other hand, they do little for anergic states where motivation and energy is lacking, and indeed, they can aggravate such conditions by worsening the apathy via the inhibitory effects that some serotonin receptors exert on the dopaminergic system.
Fortunately, serotonin reuptake inhibitors are not the only drugs available. It is ironic to note that of the neuroleptics, the most selective dopamine D2/D3-antagonists are the most beneficial with regard to motivation and initiative. More specifically, I'm referring to sulpiride and amisulpride at low doses. Indeed, there are studies suggesting that amisulpride can rival amineptine, the selective dopamine reuptake inhibitor that was withdrawn from the market for its abuse potential. The classic flupenthixol and the more recent and expensive aripiprazole are other choices among antipsychtoics that can be useful in depression, again in modest doses.
In moderation, stimulants like methylphenidate and modafinil are useful for rapidly boosting self-confidence, eloquence, coordination, memory, alertness and some other abilities, for example, this could not have been written without them. However, care must be taken in selecting a stimulant as the use of powerful neurotransmitter release inducing substances such as dextroamphetamine and methamphetamine has been associated with neurotoxicity, resulting in moderately severe dopamine deficits. Meanwhile, dopamine reuptake inhibitors are free from such toxicity and indeed, are some of the most potent neuroprotective substances in some models of Parkinson's disease, by prevention of uptake of neurotoxins into nerve terminals. Also, due to the adrenergic properties of most stimulants, adverse effects such as nervousness, and sweaty and cold distal extremities can be observed, especially in the beginning of treatment or when the dose is excessive.. The wakefulness enhancing property of stimulants can back-fire in the form of insomnia if the drug is taken too late in the day.
If the dietary restrictions are acceptable, monoamine oxidase inhibitors (MAOIs) can be powerful and appropriate choices for one's antidepressant needs. Their combination with stimulants is usually described as a recipe for disaster, but when MAOI monotherapy has proven insufficient and caution is observed, the augmentation with a stimulant can be an excellent way to boost efficacy (the combination wth serotonergic drugs, however, is hardly ever advisable). A distinction must be made between the hydrazine-based MAOIs and others, as the former also have GABAergic properties and are prone to stimulate appetite and give rise to obesity. Although the GABAergic property of for example phenelzine can be beneficial in states of anxiety, cleaner agents are usually preferable. Tranylcypromine, and in higher doses, selegiline and rasagiline, are non-hydrazine-based MAOIs with a more favourable adverse effect profile.
Even opiods can play a role as useful psychopharmacological tools, as they have powerful antidepressive, anxiolytic and antipsychotic properties. They produce somnolence initially, but within days of continued use, one can often observe a stimulating effect with enhanced motivation and energy. For example, I know of a case of chronic depression where long term methylphenidate could be terminated after initiation of morphine. While opioids are best reserved for selected, treatment-resistant cases, contemporary society is unfairly prejudiced to this class of drugs - mainly due to the perceived addiction potential or due to faulty comparisons with more deleterious substances such as alcohol. Addiction to opioids does not necessarily take place more readily than with alcohol, barbiturates and benzodiazepines, and unlike the latter three, opioids don't cloud the intellect or impair judgement and their withdrawal syndrome, while unpleasant, is not life threatening and can be mitigated with alpha2-adrenergics, baclofen (and thus phenibut) and other agents. Furthermore, not all opioids are alike, but there are differences in their duration of action and receptor-binding profiles. For example, the dysphoriant, psychotomimetic, dopamine-downregulating kappa-opioid receptor is stimulated by butorphanol but blocked by buprenorphine, which is incidentally one of my favourite smart drugs, as it not only improves working memory, but combines synergistically with stimulants and aids in weight loss; alas I must admit that it is devoid of analgesic effect, unlike paracetamol or ibuprofen. There is also great inter-individual variation with opioids, and while it is well known that a substantial percentage of users lose control of their consumption and become hopelessly addicted, it is also true that another substantial percentage of users dislike the opioid experience so much that they prefer to have pain rather than take an adequate dose of narcotic painkillers. Still the greatest problem of all is likely to be the acquisition of these remedies.
Although tolerance is most well know in association with opioids, stimulants and other "abusables", it also occurs with other agents. For example, while buprenorphine produced little tolerance and no dependence after months of daily intake, the most rapid development of tolerance I've seen was with antipsychotics and pramipexole, which is a dopamine D3/D2-receptor direct agonist used primarily in the treatment of Parkinson's disease. To be fair, on the other hand, one should consider that pramipexole and another dopamine direct agonist, ropinirole, have shown remarkable anti-anhedonic potential; and in my case, pramipexole was the only, briefly effective relief from anhedonia encountered since the beginning of my depressive illness in the previous millennium. Indeed, even in the severe dopaminergic deficit of Parkinson's disease, dopamine agonists have occasionally proven too powerfully anti-anhedonic, producing behaviours of compulsive and pathological pursuit of pleasaures such as gambling, sex and food.
In summary, the growing psychopharmacological armamentarium includes a selectioon of vastly diverse tools, none of which are without either benefits or risks and disadvantages. It's best if one can live a healthy life without them, but it's worse to suffer merely for lack of information on available options, or for fear of what people would say if they knew which tools you were using.
Edited by alpha2A, 31 March 2010 - 07:10 PM.
LongeCity
