Saturday, May 30, 2009

Modafinil: An alternative treatment for ADHD and comorbid substance abuse?

Can Modafinil (Provigil) Replace Stimulant Medications in Adult ADHD where stimulant drug abuse is a concern?

It is a Catch-22 of the ADHD world. An individual is suffering from severe ADHD symptoms and appropriate stimulant medications may help remedy some of the negative side effects of the disorder. However, due to the high prevalence of substance abuse in ADHD (some officials put the rate of comorbid substance abuse as high as to 30% in the ADHD population), including stimulant medications such as amphetamines, treatment of ADHD symptoms via stimulant medications cannot, by nature of the comorbid substance abuse disorder, be a treatment option.

The appearance of (relatively) novel non-stimulant medication alternatives such as Strattera (atomoxetine), have offered individuals with ADHD another treatment alternative. However, the results are often mixed. Strattera often works well with the inattentive-dominated forms of the disorder, but the positive results are often not as pronounced for the more hyperactive or impulsive forms of ADHD, especially if comorbid disorders such as conduct-related issues surface.

Another alternative may be a completely different type of drug, which, while not a stimulant in its own right, can act on or exhibit pseudo-stimulant properties. It appears that in at least some cases, Modafinil (Provigil) may be the type of drug we're looking for in these cases.

**Blogger's note: The extent of the study highlighting this case for Modafinil treatment for ADHD and comorbid amphetamine abuse is intended for adult treatment only. Given the relative scarcity of research on medication options for adult ADHD symptoms (compared to those designed more for children), this post is designed for offering a possible treatment alternative for ADHD in adults. Nevertheless, some recent studies have shown promising results of Modafinil as an ADHD treatment method for children and adolescents.

It is important to note, that while not initially designed as an ADHD-specific medication (and not a stimulant in its own right), Modafinil does share at least some degree of overlap with several stimulant agents for ADHD treatment. One is its regulation of catecholamines (important neuro-signaling chemical agents, whose balance in and out of neuronal cells is crucially important for regulating attention, hyperactive and impulsive behaviors, and locomotor control). As far as its mode of action and metabolism (clinical pharmacokinetics of Modafinil) are concerned, drug-drug interactions between Modafinil and several ADHD stimulant medications such as methylphenidate or dexamphetamine (Dexedrine) appear to be limited.

A background note on addiction potentials of ADHD drugs: This section is an aside, and is meant to serve as some background information and to clear up potential confusion surrounding ADHD medications and their addiction potentials. The next four paragraphs may be skipped if you are pressed for time.

While I cannot stress enough the importance of regulating neuro-chemical balance for both the onset of ADHD as well as drug addiction (which are affected by pharmacological agents such as ADHD medications, in varying forms), it is the rate of action for which these chemical changes take place which typically drives a particular drug's addiction potential.

Unfortunately, this last fact is often lost in much of the literature surrounding ADHD treatment (especially those which promote non-pharmaceutical treatments for the disorder). For example, many "natural" ADHD treatment books and websites frequently start out by asserting (erroneously) that methylphenidate is the equivalent of crack cocaine, and promotes later drug abuse and addiction.

While this blogger is a personal advocate for natural approaches to treating ADHD whenever possible (and without compromising overall treatment effectiveness in ADHD treatment), he wants to make it clear that significant differences do exist between ADHD medications and stimulant street drugs. One of the most telling signs of this is the rate of uptake and clearance of drug-like agents into and out of the brain, respectively. In general, the quicker a substance is taken up into the central nervous system and the faster it clears the brain, the more likely this chemical agent will elicit a "high" and an increased tendency towards substance dependence.

ADHD medications like Ritalin, while having some degree of overlap in structure and net effects of action as cocaine, are specifically designed to have a much slower rate of release and clearance, significantly reducing their abuse potential compared to cocaine. We have previously discussed Ritalin (methylphenidate) vs. cocaine addiction potentials in earlier posts.

Modafinil: Modes of action and addiction potential:

The reason I am providing all of this information is the fact that the successful regulation and softening of rapid spikes and clearances of chemical peaks is a crucial component to curbing the drug addiction process. It is believed that modafinil may work so well at reducing drug cravings by targeting this very mechanism. Unlike many stimulant medications which can produce some type of "high" (especially if abused by snorting or injection, or taken at abnormally high doses), Modafinil has a low abuse potential, and offers several other advantages over methylphenidate.

Modafinil does have a relatively positive track record for mitigating substance abuse disorders. For example, the administration of Modafinil can attenuate cocaine dependence. In contrast, methylphenidate (Ritalin, Concerta, Metadate, Daytrana), while being very effective as an ADHD treatment, does little to curb comorbid substance abuse disorders in ADHD patients. Unfortunately, the effectiveness of Modafinil on treating comorbid substance abuse disorders in individuals with ADHD may be limited to specific drugs. For example similar positive effects of Modafinil on nicotine dependence appear to be less pronounced.

Modafinil may also offer advantages over traditional stimulants as well. As a cognitive enhancement type of pharmacological agent, modafinil may be useful in improving the work performance of adults with ADHD by improving short-term memory and visual recall, impulse control, and spatial skills (all of which are frequent deficits in children and adults with ADHD). Additionally, similar improvements were seen in individuals with schizophrenia, suggesting the diversity of modafinil's range of performance in cognitive improvement. These improvements are typically not seen in individuals unaffected by psychological disorders, further supporting the evidence that modafinil is less likely to be abused recreationally in the general population.

The potential implications of modafinil for ADHD treatment may be further reaching than the details outlined in the original article (and basis of this post, highlighting the effects of modafinil on amphetamine abuse in adult ADHD). For example, modafinil, as a vigilance-promoting medication, can offset an afternoon dip in arousal state (which has implications on many of the shorter-acting stimulant medications, which begin to wear off around this time). This may be useful for individuals with sleep disorders (which are common in ADHD), as well as regulating circadian rhythms. In a post earlier this month, we investigated the relationship between ADHD and seasonal affective disorders, and hinted at the association between ADHD and disruption in circadian rhythms.

Potential future implications of Modafinil as an ADHD treatment alternative:

Additionally, while Modafinil may offer benefits for the whole ADHD spectrum, this blogger hypothesizes that it may be most useful for treating the inattentive subtype of the disorder. Some reasons for this are as follows:
  • Activity patterns and circadian rhythms may often be associated with ADHD subtype. For example, "morning people" with ADHD may have a tendency to fall into the more hyperactive/impulsive group, while "eveningness" is more of an inattentive ADHD trait, suggesting more of a disruption in the circadian rhythms of inattentive ADHD'ers.
  • Additionally, non-stimulants often have somewhat of a better track record with the inattentive subtype of ADHD compared to the more hyperactive/impulsive subtypes. The uses of the non-stimulant atomoxetine (Strattera), highlight this general trend. While atomoxetine treatments often result in drastic improvements in all ADHD subtypes, negative side effects are often less seen in the inattentive subtype.
  • Compared to stimulants, non-stimulant medications for ADHD often do a better job at not exacerbating comorbid disorders such as obsessive compulsive or anxiety disorders (which are often more common to the ADHD inattentive subtype). Additionally, Modafinil treatment can be useful in treating adults with ADHD and a history of mood disorders.
  • Modafinil offers advantages over methylphenidate as far as fewer side effects including appetite suppression, sleep disturbances and heart rate dysfunction (orthostatic tachycardia, which essentially is significant changes in heart rhythms based on postural changes, such as standing up quickly from a seated position).
  • Anecdotal evidence, as noted by the Modafinil and amphetamine abuse study mentioned earlier, also suggests that Modafinil may be a useful treatment method for "refractory" cases, or individuals who have consistently shown poor response to other treatment medications and interventionary measures.
  • Finally, it is important to note (and this was also touched on in the Modafinil and amphetamine abuse study), that Modafinil treatment may be better suited for the more "controlled" abusers of stimulants. In other words, better effects might be seen for adults who regularly take illegal stimulant drugs such as amphetamines as a conscious effort to "self-medicate" for their ADHD, as opposed to an out-of-control drug addict who craves the drugs on a non-scheduled basis.
Given the high propensity of comorbid disorders when deciding on treatment for ADHD, as well as practicality issues concerning the administration of medicinal agents for treatment of the disorder in adults, I see a fair amount of potential for Modafinil's "off-label" usage as a treatment alternative to stimulants in adults with ADHD.