Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Saturday, December 11, 2010

Resistant Cases of Depression and the Medicalization of the Human Condition

The monoamine based classes of modern day antidepressants include some of the most widely over used and over rated agents for treatment of depressive and anxiety disorders. This broad class of psychoactive drugs includes:
  • Selective Serotonin Reuptake Inhibitors (SSRI drugs)
  • Monoamine Oxidase Inhibitors (MAOI drugs)
  • Tricyclics (TCA drugs, or tricyclic antidepressants)
The tricyclic class of antidepressants were the originally used 'gold standard' in depression pharmacotherapy, but come with a range of bothersome side effects (not to mention toxic concerns). The MAO class works through a slightly different mechanism than the SSRI class to achieve the same goal of increasing synaptic serotonin levels; but come with extreme diet restrictions and a dangerously high likelihood of adverse interactions (with other substances). The MAO inhibitors, unlike SSRI drugs, are highly unselective. For these reasons, SSRI drugs are perhaps the most commonly used by psychiatrists, internists, and family practitioners in treating mood and impulse disorders.

Those with a history of occasional or regular opioid use present a challenge in terms of succesfully treating depression and anxiety. Much of the opioid user population is predisposed to mood disorders, and in effect either consciously or sub-consciously self medicate with opioids. Severe depression, anxiety and panic disorder, OCD, and suicide attempts are common and likely in this population. It is no coincidence that severely distressed beings are drawn to this class of chemicals, and also no coincidence that the opioids, temporarily, alleviate symptoms of severe depression and anxiety; mu and delta opioid activity mediate an increase in dopaminergic activity - a trait which opioids share with certain drugs of the antidepressant class:

Now looking at it the other way, SSRI class drugs used in treating depression have been shown to have positive effects on endogenous opioid peptide production (production of natural chemicals in the body which block pain and suffering - the bodies natural opioids)

In addition, opioids work by decreasing neuronal excitability - this is achieved in part through their inhibitory effect on the Locus Coeruleus. This specific function plays a primary role in their anxiolytic (anti anxiety), stress reducing properties.

I believe that the specific targeting of serotonin in the treatment of severe depression does little to effectively eliminate symptoms; this may be evidenced by the very modest (low) response rates of most SSRI and MAOI drugs; especially when you contrast this low response with the much better response of dopaminergic agents - which may include psychostimulant drugs such as methylphenidate and dextroamphetamine, as well as slower acting, less selective/specific drugs such as bupropion and modafinil.

It may be important to mention the drug Sertraline, of the SSRI class. Sertraline is unique among its class in that it shows significant affinity for the dopamine transporter; acting as a dopamine reuptake inhibitor in addition to its effects on serotonin. Sertraline (known by the brand name Zoloft) I believe may be somewhat effective in treating cases of severe depression in the opiate addict population - in fact, this could extend to apply to a large population of comorbid addictive/depressive cases.

In addition to Sertraline: Bupropion (Wellbutrin), Venlafaxine (Effexor), Modafinil (Provigil), and Tramadol (Ultram) have unique properties which will likely suit them for the treatment of comorbid addictive/depressive cases.

As discussed in earlier blog entries, dopamine plays a crucial role in the mechanism underlying true addiction and compulsive behaviors; which include drinking, gambling, anorexia, drug use, shoplifting and hoarding.

On a final note: Let me make it clear that I do not support the progressive 'medicalization' of any and all human behaviors which differ from the norm; I believe the brain chemistry and personality traits of every individual are unique in all cases, and when looking at the brain 'under a microscope' so to speak; there will always BE a patho-neurological/biological mechanism behind each and every human behavior - 'Different', even when explained pathologically, does not constitute a clinical diagnosis of an 'illness' or disorder... At least not in every case. A new 'illness' will be invented every so often; I believe, eventually to the point where there is not a single man woman or child in the world who is not diagnosed with some obscure list of ailments.

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