A PHYSICIAN’S PERSPECTIVE on ADHD Medications by Theodore Mandelkorn, MD – 2011
PART TWO: OVERVIEW OF MEDICATIONS
It is important to note that medical treatment should always be given for the entire waking day, seven days a week. There are few medical conditions that we do not elect to treat in the evenings, on weekends or holidays. No one chooses to turn down their brain chemistry during his or her wakeful hours. Therefore, all medical treatment for ADHD should last for at least 12-16 hours daily. With this in mind, I have highlighted (***) the medications that should be preferred treatments for ADHD.
- ATOMOXETINE, 24 HOURS (Strattera)
- CLONIDINE, TABLETS: 4-5HOURS, PATCH: 5-6 DAYS (Catapres)
- GUANFACINE LONG ACTING (Intuniv)
STIMULANT MEDICATIONS: OVERVIEW, SAFETY PROFILE, SIDE EFFECTS
- METHYLPHENIDATE TABLETS, 2-4 HOURS (Ritalin)
- DEXTRO-METHYLPHENIDATE, 4-6 HOURS (Focalin)
- METHYLPHENIDATE SUSTAINED RELEASE, 6 HOURS (Ritalin SR20)
- METHYLPHENIDATE LONG ACTING, 8 HOURS (Ritalin LA)
- METHYLPHENIDATE CONTROLLED DISPENSE, 8 HOURS (Metadate CD)
- METHYLPHENIDATE EXTENDED RELEASE, 12 HOURS (Concerta)
- METHYLPHENIDATE TRANSDERMAL SYSTEM, 12 HOURS (Daytrana)
- DEXTROAMPHETAMINE TABLETS, 4 HOURS (Dexedrine, Dextrostat)
- DEXTROAMPHETAMINE SPANSULES 6 HOURS (Dexedrine)
- AMPHETAMINE SALTS TABLETS, 6 HOURS (Adderall tablets)
- AMPHETAMINE SALTS EXTENDED RELEASE, 12 HOURS (Adderall Xr and generic)
- LISDEXAMFETAMINE, 12-14 HOURS (VYVANSE)
Guanfacine, Extended Release (Intuniv)
This new formulation of an existing medication, guanfacine, was released by the FDA to the market in Dec. It is an alpha 2 agonist, which will have a 24-hour effect on ADHD symptoms and may be beneficial for individuals with ADHD, particularly those with significant mood, anger, oppositional symptoms. Preliminary results show that it is clearly beneficial for some patients without the adverse side effects often seen with other ADD medications.
Form: Pills: 1mg, 2mg, 3mg, 4mg. Pills must be swallowed. They must not be crushed, chewed or broken or they will loose the 24-hour effect.
Dosage: It has a very slow rate of onset and will take 3-4 weeks to assess effectiveness. The primary side effect is tiredness, lethargy, and it must be started slowly. Suggest starting dose of 1 mg for one week, and raise by 1 mg each week to reach good therapeutic effect. The effects do last 24 hours.
SideEffects : Lethargy, tiredness, dry mouth, constipation, dizziness, decreased blood pressure.
Pros: A non-stimulant medication that appears to have a good, positive effect on ADD and oppositional symptoms that lasts 24hours with reduced side effect profile, compared to the traditional treatments.
Cons: A new formulation with minimal time on the market to truly assess effectiveness.
ATOMOXETINE 24 hours (Strattera)
This is a medication for ADHD, which was released by the FDA in December 2002. It is a non-stimulant medication, which is not abusable and can be written without Schedule II restrictions. This is the first medication that lasts 24 hours and therefore gives full therapeutic effect throughout the day and night .Unfortunately, over the past few years, it has not performed as well as expected. It tends to often have side effect and does not deliver as robust a response as the stimulants.
Form: Capsules: 10mg, 18mg, 25mg, 40mg, 60mg.
Dosage: Weight based dose: first four days=0.5mg/kg; target dose (day five and after)=1.2mg/kg. This medication must be taken with food to prevent nausea.
Action: Very slow acting and will take 3-4 weeks (or more) to reach a therapeutic effect. If the patient is already taking stimulant medications, suggest continuing them and adding the Strattera for the first 4-6 weeks, then tapering the stimulant slowly until discontinued.
Possible Side Effects: No long-term safety information is available for this medication. Primary side effects in children include sleepiness during the day, appetite changes, and mood or personality changes. If these occur, give the dose at night or lower the dose until they improve. Then raise dose if possible. Adults can experience more noted effects: transitory dry mouth and dizziness, insomnia, sleepiness and significant moodiness. Other effects in adults include possible bladder spasm, sexual dysfunction (uncommon but often result in discontinuation of medication). Occasionally a child or adult will get very agitated. If this occurs, discontinue the medication.
Pros: 24-hour coverage. Less effect on appetite than stimulants.
Cons: Many complaints about side effects, lack of efficacy compared to stimulants. Has not been a very satisfactory treatment for many with ADD
CLONIDINE tablets 4-5 hours, patches 5-6 days (Catapres)
Form: Patches applied to back or shoulder. Catapres TTS-1, TTS-2, TTS-3. Tablets . Clonidine tablets 0.1mg, 0.2mg, and 0.3mg.
Dosage: Very individual, usually .1-.3mg.
Action: Works quickly. Tablets work within 1 hour, patches within 1 day.
Effects: Often will improve ADHD symptoms, particularly aggressive and hyperactive behaviors. Not too helpful for focus and attention. Decreases motor and vocal tics. Can have a dramatic effect on oppositional defiant behavior and anger management. Often used as one dose at night about 1½ hours before bedtime to assist with getting to sleep.
Possible Side Effects: Major side effect is tiredness, particularly if the dose is raised too quickly. This disappears with time. Dizziness, dry mouth. Some will notice increased activity, irritability.
Pros: Excellent delivery system if patch is used. No pills required
Cons: Does not usually work as well as stimulants. Patch can cause skin irritation in many individuals and may not be tolerated. Can affect cardiac conduction (heart rate and rhythm) in high doses and must not be left around for animals or small children to accidentally ingest.
Some general comments can be made about stimulant medications as a class of medications. The longer acting medications have clear advantages over the short acting medications, not only in duration of therapeutic effect throughout the day, but also in smoothness of the therapeutic effect. It is very difficult for an individual with ADHD to remember to take multiple doses of medication during the day. Multiple dosing increases the risk of missing doses, which results in the return of symptoms at inopportune times. The afternoon dosing is frequently missed, causing significant difficulties. Furthermore, each additional dose serves as an unnecessary reminder that treatment for this condition is needed and “something is wrong.”
The reason for medical treatment is to “normalize” the day. My general rule is to always use 12-16 hour medications unless they are not effective or have intolerable side effects. In such a case, the six or eight hour medications should be tried, because some individuals tolerate them better and find them more effective. However, if the six or eight hour medication is used, a second dose should be given to allow patients to have the therapeutic benefit for the full day.
The stimulant medications are one of the most studied treatments in the history of medicine. The medications have been used extensively in children and adults over the past 50 years with no evidence to date of long-term concerning side effects. At this time there is no conclusive evidence that use of stimulants causes any long term lasting effects on growth, although there may be some delay in height and weight gain in some individuals.
The short acting stimulants are extremely abusable and are valued highly on the street. It is best to always use the long-acting preparations, which are not abusable to avoid the temptation of misuse and abuse.
There have been recent concerns expressed by the FDA and the press with regard to the use of stimulant medications and the risk of sudden unexpected death. This concern was a consequence of a study done in 1999-2003 in which they looked at a large number of individuals taking stimulants and felt that there may be a slight risk. As reported in an excellent article in the New York Times Feb 14, 2006 the apparent calculated risk of sudden unexpected death in those using amphetamines was 0.35/million (1 in 3 million) prescriptions and the risk for those on stimulants was 0.18/million (1 in 5 million) prescriptions. There is no real evidence that this is any different from that which occurs in the normal population. These extraordinary events of unexpected death tended to occur in individuals with congenital cardiac defects. For this reason, the FDA issued a BLACK BOX warning to all physicians that stimulants should be used very cautiously or not at all in individuals with congenital cardiac defects.
COMMON SIDE EFFECTS:
The following side effects are often noted with the use of stimulants. In general, side effects with the short-acting medications are more pronounced and bothersome than with the long-acting medications. Thus, long acting meds are somewhat more tolerable for long-term treatment and are certainly a marked improvement for long-term therapeutic effect.
Appetite suppression: Most will note decreased appetite during the effective hours of the medication. This often means minimal lunch intake. I suggest a small protein lunch such as milk, peanut butter crackers, beef or turkey jerky to get through the day. A milkshake after school helps. Many find their appetite returns late in the evening (around 8-9pm) when their medication wears off, and they need to be allowed to eat at that time. If weight gain is a continued concern, I often add cyproheptadine (Periactin) 4mg, ½ tablet at breakfast and dinner. Periactin is an antihistamine similar to Benedryl, which enhances appetite and often results in 1-2lbs-weight gain per month. Remember that good nutrition is helpful for all, and these individuals should emphasize protein intake in their diet.
Sleep disturbance: Many ADHD individuals will have sleep difficulties before they begin their medical treatment. At night, their brain continues its activity and starts thinking of the day. Using stimulant medications may either improve or worsen this problem. In those with no prior sleep difficulty, stimulants can create significant sleep issues. ADHD individuals do not usually have a problem with sleeping through the night (sleep disorder) but often do have problems with starting the sleep. A clear-cut bedtime routine helps (bath or shower and then read in bed) with the elimination of caffeine, computers, computer games and television at least one hour before bedtime. Interestingly, adding stimulant medication actually allows a percentage to sleep better at night, and this technique should be tried. It only takes one night to see if a dose of short acting stimulant will enable sleep initiation.
Some patients, however, require more assistance. Many patients will use a small dose of Clonidine tablets given one hour before bedtime to help with sleep initiation. Clonidine is a mild sedative, not a sleeping pill, and it is non-addictive. Approximately 60-90 minutes after taking the medication, a brief sleepy phase will occur that lasts about 20 minutes. If the patient is in bed and trying to go to sleep, it is very effective. It will NOT make someone stop playing computer games and go to bed.
Mood changes: One of the biggest complaints about stimulants is that they can cause mood changes. These come in a number of different forms.
Rollercoaster effect: Short acting medications have a continuous cycling of the blood level, either rising or falling throughout the day. This can lead to significant mood changes, particularly at the end of the four-hour cycle when the medication is wearing off. This problem with cycling is greatly diminished with the use of eight-hour and twelve-hour medications.
Rebound effect. Stimulants can often wear off very rapidly, and in some individuals, this can cause a rebound, a marked change in demeanor often characterized by irritability, loss of patience, and a worsening of the ADHD core symptoms. Rebound can occur in the evening when the medication wears off and can also be evident in the morning on first arising. The morning rebound may require an early dose of immediate release methylphenidate (MPH) prior to the administration of the long-acting dose at breakfast. The Rebound effect is markedly reduced in frequency and severity in the long-acting stimulants.
Irritability and anxiety: All of the stimulants have the possibility of causing a generalized irritability, and sometimes even anger, which is not tolerable over a long period of time. They can cause anxiety and panic disorder and may aggravate existing anxiety. Often, changing from one stimulant to another will reduce this side effect, so it is worth trying different stimulants to identify the best one for each patient.
Overdose effect: When using the stimulants it is necessary to gradually raise the dose to find the most effective therapeutic level. Sometimes in doing this, one gets an overdose effect. The stimulants are incredibly safe. They have been studied for over 50 years, and there is no evidence at this time of any long-term serious complications when used appropriately for ADHD. However, if ADHD individuals take too high a dose, they will experience an overdose effect which appears as a dulling of the personality: They complain of being somewhat physically lethargic, subdued, dull, less conversational, less apt to laugh and be social. By simply lowering the dose for one day, these symptoms will disappear.
Tic Formation: All of the stimulants have the possibility of temporarily causing a tic disorder or aggravating an existing one. There is no evidence that the use of stimulant medications will cause a permanent formation of tic disorder or Tourette syndrome. Children who already have tics (10% of children have mild tics at some point in childhood) and individuals with Tourette syndrome will find a number of different scenarios with the use of medication. Approximately 1/3 will actually notice that the tics improve (lessen) with the use of stimulants, 1/3 will see no change at all, and 1/3 will find the tics worsen with use of stimulants. If the stimulants are effective and tics are worse, a medication to help control the tics is usually added to the treatment.
METHYLPHENIDATE TABLETS 2-4 hours (Ritalin IR)
Form: Short acting tablets. Methylphenidate (MPH) 5mg, 10mg, 20mg.
Dosage: Very individual. Average 5-20mg tablets every 2-4 hours.
Action: Immediate release (IR) MPH starts to take effect in 15 minutes, which is extremely helpful for some individuals. Some children need an early morning dose 20 minutes BEFORE arising in the am, followed by a long-acting medication at breakfast. Often used as a booster for evening coverage.
Possible Side Effects See above
Pros: Very easy to use for short periods of coverage, such as early morning and evening.
Cons: Must be administered frequently during the day (3-5 times/day). Inconvenient to use at school and work. Often causes rebound and rollercoaster effect. Very abusable.
DEXTRO-METHYLPHENIDATE 4-6 hours (Focalin)
8-12 hours (Focalin XR)
Focalin is an isomer product of methylphenidate. Methylphenidate is composed of two mirror-image molecules, and it has been determined that the right-hand side of the molecule contains most of the therapeutic activity. Therefore the left-hand side has been eliminated, giving a cleaner formulation of methylphenidate.
Form: Tablets: 2.5mg, 5mg, and 10mg. (Focalin)
Capsules: 5mg, 10mg, 20mg
Dosage: The same as methylphenidate, but divide the dose by half.
Action: The same as methylphenidate, but in some individuals up to 6 hours duration.
Possible Side Effects: Same as MPH but possibly to a slightly less degree.
Pros: A cleaned up version of MPH that may last a bit longer with slightly decreased side effects.
Cons: Same as MPH. Very abusable.
METHYLPHENIDATE SUSTAINED RELEASE 6 hours (Ritalin SR20)
Replaced by Ritalin LA.
METHYLPHENIDATE LONG ACTING 8 hours (Ritalin LA)
Form: Capsules: 20mg, 30mg and 40mg.
Dosage: Very individual. Average: 20-40 mg daily or twice a day, every 8 hours.
Action: Same as methylphenidate, but eliminates the noontime dose.
Possible Side Effects: See above.
Pros: Eliminates midday dosing. Works more smoothly than IR methylphenidate and is more effective than methylphenidate SR.
Cons: Only works for eight hours and therefore subjects the patient to loss of focus and control in mid-afternoon. This requires an afternoon booster to be administered.
METHYLPHENIDATE CONTROLLED DISPENSE 8 hours (Metadate CD)
Form: Capsules: 20mg (10mg and 30mg to be available in 2003)
Dosage: Very individual. Average: 2-3 capsules in the am.
Action: Same as methylphenidate.
Possible Side Effects: See above.
Pros: Works more smoothly than IR methylphenidate. Sometimes is effective when Concerta and Ritalin LA are not effective. Not abusable.
Cons: Works for only eight hours. (See Ritalin LA)
***METHYLPHENIDATE EXTENDED RELEASE 12 hours (Concerta)
No generic available
Form: 12-hour long-acting tablet uses a unique delivery system that delivers a constant therapeutic level of methylphenidate for twelve full hours. Cannot be broken or cut or delivery system is destroyed. Concerta 18mg, 27mg, 36mg, 54mg.
Dosage: Dosage will vary as with all methylphenidate products.
Concerta 18mg = Ritalin 5mg three times a day
Concerta 27mg = Ritalin 7.5mg three times a day
Concerta 36mg = Ritalin 10mg three times a day
Concerta 54mg = Ritalin 15mg three times a day
Action: 12 hours of consistent therapy with no highs or lows throughout the day. A few individuals will only get 8-9 hours of effective therapy and will need either a higher dose or a second dose.
Possible Side Effects: See above.
Pros: Unique delivery system (an internal osmotic pump) avoids multiple dosing throughout the day. No dosage at school. No rebounding with missed doses. Fewer side effects, less mood swings, and a better therapeutic response for many individuals. No daytime dosing. Less anxiety and worry. Not abusable.
Cons: Does not work for all individuals who use methylphenidate. If ineffective, should try Ritalin LA and/or Metadate CD. May need a short-acting booster to cover the evening hours.
METHYLPHENIDATE TRANSDERMAL SYSTEM 12-15 HOUR (Daytrana)
No generic available
The trans-dermal patch arrived on the market July of 2006 as a new and novel delivery system for methylphenidate. The patch has the medication within the adhesive layer and is thus very thin. It works by diffusion, allowing the medication to gradually diffuse through the skin into the blood stream directly, thus avoiding the intestinal tract. It is designed to be worn for nine hours and then removed, but will last longer if needed for evening activities. After removal it will gradually lose effect over the next three hours, thus giving extended and controlled hours of therapy as the day dictates. The unique attribute of the patch is that the patient has complete control of when to start the patch and when to discontinue the patch. For the first time, the patient can regulate the treatment for part or all of the day. The medication in the patch is methylphenidate, and thus all of the above information regarding this medication applies.
DEXTROAMPHETAMINE TABLETS 4 hours (Dexedrine, Dextrostat)
Form: Short acting tablets 5mg, 10mg.
Dosage: Very individual. Average 1-3 tablets each dose every 4-5 hours.
Action: Rapid onset of action, approx. 20 min. Lasts 4-5 hours.
Possible Side Effects: See above.
Pros: Excellent safety record. Rapid acting. Some patients who do well on dextroamphetamine prefer the tablets to the spansules. The rapid onset in tablet form is apparently more effective for these individuals.
Cons: Same as MPH. Very abusable.
DEXTROAMPHETAMINE SPANSULES 6 hours (Dexedrine)
Form: Long acting. Dexedrine Spansules 5mg, 10mg, 15mg.
Dosage: Very individual. Average is 5-20 mg.
Action: Very individual. May take up to one hour to be effective. Usually lasts 6-8 hours. In some individuals, it may last all day. In others, it may only last 4 hours. Most will take twice a day, six-hour intervals
Possible Side Effects: See above
Pros: Excellent safety record. May be the best drug for some individuals. Long-acting, smooth course of action. May avoid lunchtime dose at school.
Cons: Slow onset of action. May require a short acting medication at the start of the day. Very abusable.
AMPHETAMINE SALTS TABLETS 6 hours (Adderall)
Form: Long acting tablets: 5mg, 7.5mg, 10mg, 12.5mg, 15mg, 20mg, 30mg.
Dosage: Very individual, usually between 5mg and 20mg, once or twice each day.
Action: Usually lasts 6 hours. May be given once or twice a day depending on the length of therapeutic effect. Duration of effect varies from person to person.
Possible Side Effects See above.
Pros: Only needs to be given once or twice a day. Often fewer side effects than the short acting medications.
Cons: Can cause irritability in a small percentage of patients. Very abusable.
***AMPHETAMINE SALTS EXTENDED RELEASE 12 hours (Adderall XR)
Generic available April 1, 2009
Form: Uses a unique delivery system that delivers a constant therapeutic level of amphetamine salts for twelve full hours. Capsules: 5mg, 10mg, 15mg, 20mg, 25mg, 30mg.
Dosage: Very individual. Average 15-30mg daily.
Action: Long-acting 12-hour control of ADHD symptoms for coverage during most of the day.
Possible Side Effects: See above.
Pros: Very effective. Same as Adderall with longer duration of action. Cannot be abused.
Cons: May need a booster to cover the evening hours.
LISDEXAMFETAMINE 12-14 hours (Vyvanse)
No generic available
Form: A Pro-drug which renders this delivery system minimally abusable. A new and novel delivery system which will deliver dextro-amphetamine smoothly over a 12-14 hour period.
Dosage: Capsules: 30mg, 50mg, 70mg
Action: The same as Dextroamphetamine
Side Effects: Same as Dextroamphetamine
Pros: The only long-acting Dextroamphetamine on the market, and very unlikely to be abused.
Cons: Same as stimulants
For the introduction to this article, please see: PART ONE: Therapeutic Treatment of ADHD
For an excellent reference book regarding all of the medications that might be used for ADHD individuals, including not only medications for ADHD but also medications for all of the associated co-morbid conditions, please refer to the following book:
STRAIGHT TALK ABOUT PSYCHIATRIC MEDICATIONS FOR KIDS , Revised Edition 2004
by Timothy Wilens M.D.
About the author:
Reprinted with permission from Theodore Mandelkorn, MD, a physician with Puget Sound Behavioral Medicine, a clinic that treats teens, children and adults with attention deficit disorder and related conditions. For further information visit the website at http://psbmed.com, or call 206/275-0702.