ADD and ADHD

Fresh Day For ADHD

ADHD treatment evolves: This will be a short note to quickly address the growing comments here at CorePsych Blog on the previous Intuniv post.  There I discussed reports on the differences between Tenex and Intuniv, now I have seen the action in my office. Tenex, generic name guanfacine, has been used for years with specific good effect to manage and treat the angry and irritable individuals with ADHD – the Oppositional and Defiant.

Remember: Intuniv is not a stimulant – refills on prescriptions will not be so problematic.

Intuniv Audio Reports At CinchCast:

My last Cinch Recording, already Tweeted out, tells you in about 2 min the details on Intuniv dosing strategy, and I will also outline them here. Listen to my comments on the other CinchCast recordings on Russell Barkley and Amy Arnsten from Yale.

The Differences Between Tenex, Intuniv, and Clonidine

1. Tenex has a shorter half-life, and often requires at least twice a day dosing.
2. Intuniv is once a day, and, interestingly often remains effective for irritability in the next AM – coming up to my favorite subject DOE [Duration of Effectiveness]: in this case – 24 hr!
3. Tenex has peaks and valleys of effectiveness with dosing strategies that require significant adjustments to dial in correctly.
4. Intuniv is easier to dose: See the protocol below.
5. Clonidine is an alpha 2A agonist, encouraging the closure of the post synaptic calcium channel, but also stimulates other alpha 2 receptors [B&C], thereby creating more problems with hypotension [low BP] and encouraging sleep.
6. Interestingly, Intuniv has a significant soporific turn, but in the 12 -14 hr range often helping with sleep, without further medications in the PM and no dose necessary at noon.
7. Clonidine is not approved by the FDA for treatment for ADHD.

Dosing Strategies: Uncomplicated

1. There will be few problems with dosing as Intuniv comes closer to absolute simplicity than many of the other ADHD meds.
2. Titration: First week 1mg in the AM, second week 2mg, third 3mg and fourth week 4mg as indicated by response – highest recommended dose = 4 mg/day.
3. Bottom of the Therapeutic Window – it isn’t working – this will be self evident!
4. Top of the Therapeutic Window is determined by side effects on the forced dose study completed for FDA safety/efficacy approval – simply being soporific [sleepy] or fatigued – the two main adverse effects when the dose was pushed up [too] quickly for the study.
5. Look for an effect lasting 24 hr regarding the Sides of the Therapeutic Window. AM cranky/anger often disappears.
6. Most people were successful with the dose at 3-4mg/day, so be patient, don’t rush the increase, watch for side effects, and if it’s too much back down to the previous dose.
7. Most did well at 3mg, the dosage is often weight related, but not always [more weight-higher dose] details later.
8. A significant number are doing well at 1 and 2mg.
9. If you are coming over from Tenex, drop the dose down, start at the 1mg and work your way up.
10. Not recommended with Clonidine for bed, for obvious reasons – using more of the same type of medication.

Other FAQ and Observations

1. It can be used with Vyvanse and Methylphenidate products, more posts coming soon on this matter.
2. It has an excellent effect on simple Inattentive ADD, just for attention and is approved by the FDA for ADHD.
3. First line indications for this medication: ODD, anger, frustration, irritation, in spite of doing well on other ADHD meds.
4. For those medical teams out there looking to treat angry kids with atypical antipsychotics for “childhood bipolar” this looks like [purely anecdotal] it will be good for some of those kids who look bipolar, but are actually more ADHD with ODD.
5. Confusing presentations can still be explained by more comprehensive neurotransmitter evaluations reported elsewhere here at CorePsych Blog. Using neurotransmitter precursors to support neurotransmitter imbalances simultaneously with Intuniv show no challenges, and have worked exceedingly well with some of the most refractory kids seen in our office.
6. Incidence of hypotension in the forced dose titration trials was 6% with Intuniv, and 4% with placebo.
7. No deaths reported from guanfacine since it was launched in 1986.
8. More on the specifics of glutamate relevance as a new focus for ADHD neurotransmitters coming soon.
9. This medication is not like Strattera at all [except that it is not a Schedule II]. Strattera only effects norepinephrine reuptake at the synapse, Intuniv actually modifies/facilitates glutamate neurotransmission. Glutamate is the most prevalent neurotransmitter in the brain, with ~ 1/3 of the brain receptors = glutamate. ADHD can be corrected by enhancing flagging glutamate networks through the post synaptic activity of stimulating that alpha 2A receptor post-synaptically. More on all this, and some important drug-drug interactions soon.

My Prediction

Bipolar Redefined: This one is anecdotal, but relevant for future watchfulness: With all of the ‘bipolar’ misdiagnosis so prevalent out on the streets [identifying almost any angry mood as a primary mood disorder] – when the underlying oppositional and anger problems so often arise from the oppositional subset of ADHD, Intuniv will change treatment protocols and outcomes.

Said another way, the use of atypical antipsychotics so frequently in children and adolescents will no longer become the first off label choice – if the diagnosis is actually ADHD and treatable with Intuniv. My take: Intuniv should/will become first line for this subset. We are already seeing, both in our office and in comments from many physicians, a trend in this direction. Time will tell. Intuniv wins hands down on the safety issue, and appears, at this early juncture, to help rather remarkably with those angry moods.

Drug Interactions

1. From the package insert: Intuniv is a CYP450 3A4 substrate. It will be induced [reduced in effectiveness] by Trileptal, Provigil and Tegretol. It could accumulate, and take the patient out the Top of the Therapeutic Window with Prozac, Paxil, and Luvox all of which significantly block 3A4.
2. Suggestion here: don’t use Intuniv with these latter 3 medications at all. Prozac and Paxil, as you know from my many comments on these meds regarding the 2D6 CYP450 pathway, regularly create unpredictable outcomes with stimulants – and over here on the 3A4 [I think I'm on an LA freeway ] they are still dirty drugs. This drug interaction duo should be on your ADHD medication radar, and off your list for patient care. If you are on the Trileptal group of inducers, expect a significant accumulation when you discontinue any of these as your dose may have been higher as a result of this induction process.

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