Tuesday, July 22, 2014

Learning and Behavior Series Part 5: Medications

This is the 5th post in a series of blogs on Learning and Behavior. It will focus on prescription treatments used primarily for ADHD.

There are many parts to the treatment of ADHD including behavior modifications; school accommodations; optimizing nutrition, sleep, and other healthy habits; and supplements -- all covered in previous posts in this series. This one will cover common medications that have been approved or are commonly used for the treatment of ADHD. I am not going to go into how to diagnose ADHD here, but it is of course of utmost importance to have the correct diagnosis before medication is considered.

There are many treatments out there that are not approved for the purpose being used, but if done properly might be a good consideration. Physicians sometimes use treatments that have not been approved for the purpose because they know from experience that it works or they are at a loss from approved treatments failing and they need to try something else.
One example is using a shorter acting form of guanfacine (Tenex) that has not been approved to treat ADHD, but is less expensive than the longer acting form (Intuniv) that is approved for ADHD.

Another common example is the use of albuterol, a medicine that helps breathing with conditions that cause wheezing. It is not approved for use under 2 years of age, but it is commonly used for younger children with difficulty breathing -- and it helps them breathe, which might keep them out of the hospital and off of supplemental oxygen.

I do not think that all non-approved medicines are good or bad. It is a very individual decision of what medicines to use. Discuss with your doctor if a treatment is approved or if they are using something that is not. Although this is relatively common among people who treat children because many drugs have not been tested in children and have been "grandfathered" into use through experiences that show benefit, be sure the provider is not picking something that has no basis or supporting evidence, especially if he or she profits from the treatment.

Be very wary of anyone who promises a cure - if one really existed everyone would use it.

Medications approved to treat ADHD

Medications to treat ADHD fall into the following categories:

  • Stimulants
  • Methylphenidates (Ritalin©, Focalin©, Concerta©, Daytrana©, Metadate©, Quillivant©

  • Amphetamines (Adderall©, Vyvanse©, dexedrine) 

  • Non-stimulants
  • Atomoxetine (Strattera©
  • Guanfacine (Intuniv©
  • Clonidine (Kapvay©
  • Others are used off-label (no FDA approval for the purpose of ADHD treatment): Tenex, Catapres patch, antidepressants, and antipsychotics

When a medication is needed to control symptoms of ADHD, the first line medications are the stimulants unless there are contraindications. Non-stimulant medications are not found to be as effective as stimulants in the majority of children, but they do have a place in the treatment plan for some children. They are sometimes used in addition to stimulants for optimal results. For information on how these medicines, see A Guide to ADHD Medications. It reviews how stimulants act on dopamine and norepinephrine and various time release patterns of different medicines.

Side Effects

Parents usually worry about medication side effects, which is a very legitimate concern. Overall the medicines listed above are very well tolerated. If a child has side effects to one stimulant, they can usually do well on a different class (methylphenidate vs amphetamine). I often hear concerns that parents don't want their kids changing their personalities or becoming "zombies". If the right medicine is used at the appropriate dose, this is usually not a problem. Finding that right medicine and right dose might take some trial and error, but work with your prescriber to get to the right one for your child.

The most commonly observed side effects of stimulants are:

  • Decreased appetite – Appetite is often low in the middle of the day and more normal by supper time. Good nutrition is a priority, so encourage kids to eat the healthy "main course" first and leave the dessert out of the lunchbox. Short acting meds improve mid day appetite since they wear off around lunch time. Kids are often very hungry in the evenings when medicines wear off, so encourage healthy foods at that time. I have also seen some kids who have a really hard time off medicine sitting down to eat actually gain weight better on medicine because they can finish the meal.
  • Insomnia – Trouble sleeping is common with ADHD, with or without medicines. If it is due to the stimulant medicine, trouble sleeping may be relieved by taking it earlier in the day.
  • Increased irritability -- Moodiness is especially common as the medication wears off in the afternoon or evening and in younger children. It makes sense if you consider that all day they are able to focus and think before acting and speaking, but then suddenly their brain can't focus and they act impulsively. Typically kids learn to adjust to the medicine wearing off as they mature. Sometimes just giving kids 30 minutes to themselves and offering a healthy snack can help. Cognitive behavioral therapy can help. 
  • Anxiety -- Anxiety does occur with ADHD and might be under-appreciated before the ADHD symptoms are treated. When kids can focus better, they might focus more on things that bother them, increasing anxiety. It is also possible that anxiety is misdiagnosed as ADHD, which is one reason for stimulant medication failure.
  • Mild stomach aches or headaches -- Stomach aches and headaches are occasionally noted with stimulant medications. It is my experience that they are most common with a new medication or a change in dose. Because these have many causes, it can be hard to determine if they are really from the medicine or another cause. If they persist with the medicine, it might be needed to change to another.
  • Tics - Tics are related to treated and untreated ADHD. People with ADHD are more likely to have tics than the general population. It was once thought that tics were caused by the stimulant medicines, but it is now thought that they happen independent of the medicine, and medicines might even help treat the tics.
  • Growth -- Weight gain can be difficult for some kids on stimulant medications due to the appetite suppression on the medicine. Studies have shown a decreased final adult height of about 1-2 cm (1/2 - 1 inch), which most agree is not significant compared to the benefits in self esteem, academics and behavior children gain on stimulants.

Rare side effects of stimulants include hallucinations and heartbeat irregularities

  • I have only seen two children who could not tolerate stimulants due to hallucinations, but it is very scary for the family when it happens. Unless there is a significant family history of them, I don't know a way to predict which child is at risk. These are a contraindication for continuing that medication, but another type of stimulant or medication can be considered. 
  • Cardiac (heart) problems are overall a rare complication of stimulants and often times are not a contraindication to continuing the stimulant medicine. There is a small increase in blood pressure and heart rate, both of which should be monitored regularly while on treatment and if the treatment is stopped. 

A cardiologist should be considered to further evaluate a patient prior to starting a stimulant if there is any of the following:

  • Shortness of breath with exercise not due to a known non-cardiac cause, such as asthma
  • Poor exercise tolerance compared to children of the same age and conditioning 
  • Excessively rapid heart rate, dizziness, or fainting with exercise 
  • Family history of sudden cardiac death or unexplained death (such as SIDS) 
  • Family or personal history of prolonged QT syndrome, heart arrythmias, cardiomyopathy, pulmonary hypertension, implantable defibrillator or pacemaker 

Common side effects for the non-stimulants include the following:

  • Atomoxetine can cause initial gastroesophageal complaints (abdominal pain, decreased appetite), especially if the dose is started too high or if it is increased too rapidly. It can also cause tiredness and fatigue when it is first started or if the dose is increased too quickly. It can increase the blood pressure and heart rate, both of which should be monitored regularly during treatment with atomoxetine. There is an increased incidence in suicidal thoughts, though uncommon, so children should be monitored for mood issues on this medication. A rare complication of atomoxetine is hepatitis (inflammation of the liver with yellow jaundice and abnormal liver function labs). The hepatitis resolves with stopping the atomoxetine. 
  • Guanfacine and clonidine both cause fatigue and tiredness, especially when first starting the medication or with increases in dose. Clonidine is often used at bedtime to help kids with ADHD sleep. Both of these medications can lower the blood pressure and heart rate, and these should be monitored closely while on guanfacine or clonidine.

Getting Started

The first step in treating ADHD is getting a proper diagnosis. This should be done with input from parents and teachers since symptoms should be present in at least two settings. ADHD symptoms overlap with many other conditions, and if the diagnosis is not correct, medications are more likely to cause side effects without benefit. Do not jump into medication until the symptoms have been fully evaluated and a proper diagnosis is made according to DSM criteria.

Stimulant medicines are considered first line treatment for ADHD in kids over 5 years of age. There are short acting and long acting formulations available for each type of stimulant. There are advantages and disadvantages to each. Short acting medications tend to last about 4 hours, so can be given at breakfast, lunch, and after school, allowing for hunger to return as each wears off to help kids maintain weight. They are often used later in the day after a long acting stimulant wears off for teens who need longer coverage. Long acting medicines tend to last between 6 and 12 hours, depending on the medicine and the person's metabolism. The benefit is that people don't need a mid-day dosing, which for school kids means avoiding a daily trip to the school nurse, which can be socially non-acceptable for older children. It is also easier to remember once/day medication versus multiple times/day dosing. The downside is that some children don't eat well mid-day with long acting medicines.

In general it is recommended to pick one of the stimulant medicines and start low and titrate to best effect without significant side effects. Feedback on how the child is able to focus and stay on task, and reports of other behavioral issues that were symptoms in the first place should be received from teachers and parents, as well as the child if he is able. There are many things to consider that affect focus and behavior that are not due to the medicine: sleep, hunger, pain, illness, etc. It takes at least a few days to identify if the medicine is working or not or if other issues are contributing to the focus and behaviors. The younger the child the longer I usually advise staying on a dose so a parent has a chance to hear from the teacher how things are going. I usually don't increase faster than once/week. I rely more on the student's report in middle and high school, since those students can be more insightful and they have so many teachers throughout the day that most teachers are not as helpful. Older students who are in tune with their problems and how they are responding to the medicine might be able to increase every few days, as long as there are no confounding factors that could influence symptoms, such as change in sleep pattern, big test or other stressor, or illness.

Which medicine to choose?

As you see above, there are two classes of stimulants, methylphenidates and amphetamines. While some children respond better to methylphenidates, others to amphetamines, some do equally well on either, and some cannot tolerate either. It is not possible to predict which children will do best on any type, but if there is a family history of someone responding well (or not) to a medicine, that should be taken into consideration of which to start first.

Another thing to consider is whether or not a child can swallow a pill. Some of the medicines must be swallowed whole. If you aren't sure if your child can swallow a pill, have them try swallowing a tic tack. Use a cup with a straw, since the throat is narrowed when you tilt your head back to drink from an open cup. Another option is to put it in a spoonful of yogurt or applesauce and have your child swallow without chewing. If your child cannot swallow a tic tac, you can choose a medicine that doesn't need to be swallowed. Some come in liquid or chewable formulations. Some capsules can be opened and sprinkled onto food, such as applesauce or yogurt. There is a patch (placed on the skin) available for the methylphenidate group.

I would love to say that cost shouldn't matter, that we pick the medicine based purely on medical benefit, but cost does matter. Before you go to the doctor to discuss starting medicine (this or any medicine for any condition) look at the formulary from your insurance company. All other things being equal, if one medicine is not covered at all (or is very expensive) and another is covered at a lower tier, it is recommended to try the least expensive option first. Of course, if the least expensive medicine fails, then a more expensive one might be the right choice. Also check to see if a medicine requires a prior authorization, which might require that other medicines are tried first.

The ADHD Medication Guide is a great resource to look for generics (marked with a "G"), which must be swallowed whole or can be opened or chewed (see the key on page 2). The age indications listed on page 2 are those that have FDA approval at the ages listed, but there are a lot of times that physicians use medicines outside the age range listed. Some do not even have an age indication listed. These ages are due to testing results, and can be limited because one age group might not have been tested for a specific medicine. Note that the 17 year and adult medicines are different. Is there really a difference between a 17 and an 18 year old? Not likely.

Finding the right dose

It is recommended to start with one of the two main classes of stimulants with a low dose, and slowly increase to find the best dose. If that stimulant doesn't work well or has side effects that are not tolerated, then change to the other class of stimulant. If that one does not work, you can try a different medicine from the class of stimulant that worked best. If the third medicine doesn't work, then a non-stimulant can be tried. I also recommend re-evaluating the original diagnosis at this point, since ADHD might not be the cause of the issues and finding the right cause can lead to a better treatment.

Titrating the medicine goes something like this:

  • If symptoms are well controlled and there are no significant side effects, the medicine should be continued at the current dose. 
  • If symptoms are not well controlled and there are no side effects that prohibit increasing, the dose should be increased as tolerated. 
  • If symptoms are not well controlled (i.e. room for improvement) but there are side effects that prohibit increasing the medicine, consider a longer period of watching on this dose versus changing to a new medicine.

Things to consider

Time Off: Once a good dose is found, parents often ask if medicines need to be taken every day. Drug holidays off stimulants were once universally recommended to help kids eat better and grow on days off school. Studies ultimately did not show a benefit to this, and some kids really can't take days off due to behavior issues, including safety issues while playing (or driving for older kids). It also seems that when kids are off medicine they do not have good self esteem due to repeated failures, so taking medicine regularly is important to them.

When kids can manage their behavior adequately, it is not wrong to take days off. Stimulants work when they work, but they don't build up in the body or require consistent use. (This is not true for the non-stimulants, which are often not safe to suddenly start and stop.) Some kids fail to gain weight adequately due to appetite suppression on stimulants, so parents will take drug holidays to allow better eating. Days off the medicine also seems help to slow down the need for repeated increases in dosing for people who are rapid metabolizers.

Talk to your child's doctor if you plan on not giving your child the medicine daily to be sure that is the right choice for your child.

Remembering the medicine: It is difficult to get into the habit of giving medicine to a child every day. I wrote an entire blog on remembering medicines. My favorite tip is to put the pills in a weekly pill sorter at the beginning of each week. This allows you to see if you're running low before you run out and allows you to see if it was given today or not. These medicines should not be kept where kids who are too young to understand the responsibility of taking the medicine have access.

Controlled substances: Controlled substances, such as stimulants, cannot be called in or faxed to a pharmacy. They cannot have refills, but a prescriber can write for either three 30 day prescriptions or one 90 day prescription when they feel a patient is stable on a dose. Stimulants are not controlled substances because of increased risks to the individuals it is prescribed for, but because they have a street value -- teens often buy them from other teens as study drugs. This can be very dangerous since it isn't supervised by a physician and the dose might not be safe for the purchaser. It is of course illegal to sell these medicines. The DEA does monitor these prescriptions more closely than others. If the prescription is over 90 days old, many pharmacists cannot fill it (this will vary by state), so do not attempt to hold prescriptions to use at a later time.

Acids and Stimulants: It has been recommended that you shouldn't take ascorbic acid or vitamin C (such as with a glass of orange juice) an hour before and after you take medication. The theory is that ADHD stimulants are strongly alkaline and cannot be absorbed into the bloodstream if these organic acids are present at the same time. High doses of vitamin C (1000 mg) in pill or juice form, can also accelerate the excretion of amphetamine in the urine and act like an "off" switch on the med. In reality  have never seen this to be an issue. If anyone has noticed a difference in onset of action or effectiveness of their medicine if they take it with ascorbic acid or vitamin C, please post your comment below.

When Mom and Dad disagree: It is not uncommon that one parent wants to start a medication for their child, but the other parent does not. It is important to agree on a plan, whatever the plan is. Have a time frame for each step of the plan before a scheduled re-evaluation. If the plan isn't working, then change directions. If kids know it is a disagreement, they might fear the medicine or think that needing it makes them inferior or bad. Do not talk about the diagnosis as if it's something the child can control - they can't. Don't make the child feel guilty for having this disorder. It isn't fair to the child and it only makes the situation worse.

Having the medicine when you need it-- 

Refills: There is nothing more frustrating for a parent and child than to realize that there's a big test tomorrow and you have no medicine left and you're out of refills. Be sure to know the procedure for refills at your doctor's office. By federal law we cannot give more than 3 month's worth of a stimulant medicine. They cannot be called in to a pharmacy. In my office we see patients at least every 3 months (more often when starting a medicine or if changes are needed). I advise that they schedule the next appointment as they leave the office so they don't forget to schedule. I make these appointments longer than standard "sick" appointments, so it is hard to sneak one in on the same day. 
Travel: It is very important to plan ahead prior to travel. If you forget your child's stimulant, no one can call out a prescription since it is a controlled substance. You must plan ahead so that if a refill will be needed during the trip you will either be able to fill a prescription you have on vacation or you will need to fill the prescription in advance. Most people can get a prescription 7 days prior to the 30 day supply running out, but not sooner, so you might need to fill a couple prescriptions a few days earlier in the month each to have enough on hand to make it through your vacation. It takes planning! If you are out of town and you realize you forgot your child's non-stimulant, call your doctor to see if they will call it out. Many of the non-stimulants are not safe to suddenly stop, so they are likely to call it out. Insurance is not likely to pay for these extra pills though if it was recently filled. 
Lost prescriptions: We are able to give up to three prescriptions at one time, but most pharmacists will not keep the prescriptions. This means that you must know where the prescriptions are and not lose them for 3 months. Lost prescriptions are handled differently by different prescribers, but all should take them seriously due to the controlled substance rules of the DEA. If a parent reports losing them frequently, that usually leads to consequences, so be sure you know how your doctor handles this situation. I will generally allow a parent to write a letter documenting the lost prescription and I document this in the medical record in a way that is easy to see at future visits. If this repeats, I will not be able to continue to prescribe a controlled substance for that family, which only makes the child suffer. 
Mail order: Some insurance companies will allow mail order 90 day prescriptions. Some not only allow, but require them on daily medicines. Others do not allow it. In general I advise against a 90 day prescription if the dose is not established or if there are any concerns that it might not be the perfect dose. If there is any concern that it might need to be changed, a 30 day prescription is a better option. If you will need to do a mail order, be sure you schedule your appointment to get the prescription early enough to account for the lost time mailing. 

Before your visit:

Before you meet with your physician to discuss a new ADHD diagnosis or a possible change in treatment plan, be sure to get the following information and have it available at the visit or the visit will not be as productive as you desire:

  • Insurance formulary
  • Standardized testing from teachers, parents, and other significant adults 
  • Verify if your child can swallow a tic tac or pill 
  • Any contributing family history (family member responses to medications, family history of heart issues, etc)

More Quest for Health blogs on ADHD:

References and resources:

ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

ADHD Medication Guide

Parents Med Guide

Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder.

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