No treatment is 100% safe and 100% free of side-effects. Even a sugar pill can be harmful to a person with Diabetes Mellitus. Counseling can bring up anxious, sad, or angry feelings that had been buried below the surface. The goal of treatment is to provide benefits that outweigh the potential risks. Before any treatment, the potential benefits vs. risks should be carefully determined.
Picture something you want to do that is a little risky. For example, you might go on vacation with friends and have the opportunity to take scuba diving lessons. The benefits of scuba diving include allowing the sensation of swimming freely under water like fish, close to beautiful sea- life. The risks include the “bends,” (a painful and dangerous condition from surfacing too quickly), drowning, or being eaten by a shark. Your friends might not be a strong swimmers and feel instead that snorkeling will give enough enjoyment. They would therefore feel that the risks outweigh the benefits and decide not to learn to scuba-dive. You, however, might be a strong, adventurous swimmer and want to get scuba-diving certification. For you, the benefits outweigh the risks.
Taking medication is not a frivolous decision as scuba diving classes were for me.
However, the decision to take medication is also based on the risks vs. benefits. Let’s look at the risks first:
There have been many news reports about antidepressants being associated with suicidal thoughts in people younger than 25 years old. These are based on reports from the Federal Drug Administration (FDA). In 2004, the FDA issued a “black box warning” of the risks of antidepressants for young people. (A “black box” on a medication’s prescribing label means that the reader must pay careful attention to the warning inside the box. It generally makes doctors more hesitant to prescribe the medication and patients less likely to take it.) FDA scientists analyzed information from several research studies in which some minors were given an antidepressant and some were given a placebo. They found that the risk of having suicidal thoughts on an antidepressant was twice that of a placebo. However, this was a very small number absolute number- 2% of those taking a placebo developed suicidal thoughts, compared to 4% taking an antidepressant.
An important point is that patients with serious suicidal thoughts are often not allowed into research studies. However, this group does not represent the typical population of depressed young people who would be seen in a psychiatric clinic. In a typical clinic, a high percentage of depressed people would be expected to have suicidal thoughts. There is no way to tell from these studies how many young people would have decreased suicidal thoughts as a result of antidepressant treatment (Norman Sussman, Primary Psychiatry, Feb 2007).
None of the minors in the studies actually killed themselves, and to date it does not appear that antidepressants are associated with a greater risk than placebo of actual completed suicide.
To understand this concept, pretend that you’re testing out a new type of marble cleaner to make muddy marbles bright and shiny again. You throw 100 marbles into each of two circles in the dirt. You pour “Marvelous Miracle Marble Mix” onto one set of marbles and water on the other. You find, to your dismay, 4 discolored marbles from the group that was splashed by your mix, versus 2 from the group that received water. Do you conclude that your “Marvelous Miracle Marble Mix” is a bust? Not exactly- it turns out that you only used clean marbles to test your mix. You don’t know what would have happened if you had used your mix on muddy marbles.
Your hope is that more muddy marbles would have been restored to their original, shiny selves.
In fact, there is evidence to support the belief that antidepressants decrease the youth suicide risk. One study, published in 2006, examining health plan records of over 65,000 teenagers and adults, found that the risk of suicide attempts or completed suicide was highest in the month before starting antidepressant treatment, and steady decreased after starting antidepressants Simon et al., The American Journal of Psychiatry, Jan 2006). Another study examining suicide rates in children ages 5-14 across the United States found that counties with higher rates of SSRI prescriptions had lower rates of suicide (Robert Gibbons et. al., American Journal of Psychiatry, Nov 2006). Another group of investigators examined all suicides in people younger than 18 in New York City between 1999-2002. 36 out of the total of 41 youths who had committed suicide had blood test results which allowed the examiners to determine whether they had been taking antidepressants at the time of their deaths. Antidepressants were detected in the bloodstream of only one, a homeless 16-year-old male who died of an intentional drug overdose Leon et al., J. Am. Child Adolesc. Psychiatry, Sept. 2006).
Some people who take antidepressants actually do commit suicide. The most frequent explanation is that they felt suicidal because they were suffering from depression, and the antidepressants they were given unfortunately did not help them. Depression can sadly be a terminal illness, like cancer, and sometimes the best treatments do not help enough. Suicide is a shocking, devastating event for families. It is natural for families to point to the antidepressant as the possible reason. The reality is that the cause of a suicide is far more likely to be the depression than the medicine used to treat it.
Why would an antidepressant increase suicidal thoughts? We don’t know for sure, but there are several possible explanations. Some people, especially minors, can feel more restless and agitated with an antidepressant, particularly during the first few weeks of treatment. (This can sometimes be avoided by starting with a very low dose and increasing slowly.) Some people describe this feeling like “having ants in your pants,” or “an itchy feeling under your skin.” Some people have trouble falling asleep or have poor quality sleep when they start antidepressants.
Uncomfortable side effects from antidepressants may result in suicidal thoughts for some.
Some people who are given antidepressants may actually have a diagnosis of bipolar disorder. This is a more serious type of depression that used to be called manic depression. In addition to “low,” depressed moods, people with bipolar disorder can have “high” or manic moods, with impulsive, irrational behaviors. Bipolar patient who takes antidepressants may develop manic symptoms mixed in with their depression. This results in a particularly toxic form of mania called “mixed mania,” with irritable, agitated mood and impulsive actions. Such symptoms markedly increase the risk for suicidal thoughts and/or actions. (Antidepressants may sometimes safely be given to bipolar patients if they are first treated with types of medication called mood stabilizers.) Young people even without bipolar disorder have been known to become impulsive and disinhibited with antidepressants. This behavioral activation would make them more likely to act on suicidal thoughts at the beginning of treatment.
Depressed patients may have more risk for suicidal thoughts and actions in the early stages of treatment. Most often, their energy level improves before their mood does. Severely depressed people may have thoughts of committing suicide but not the energy to act on them. Therefore, when they begin to improve, they may develop the energy and motivation to commit suicide, before mood and judgement increase enough to see alternatives.
Sometimes, young people stop taking their medication without telling anyone, including the study investigators. If patients stop antidepressants abruptly, they can have withdrawal side effects, which can feel unpleasantly like the flu- agitation, headache, upset stomach, and light- headed sensation. These symptoms are not physically dangerous, but in a vulnerable person can certainly increase suicidal thoughts.
Other side effects of antidepressants can be upset stomach, headache, appetite changes, weight gain or loss, decreased sexual interest or sensation, insomnia or sleepiness, and rarely, easy bruising or bleeding. Rarely, antidepressants can lower the blood sodium level. This is called hyponatremia, and may be characterized by headaches, nausea, confusion, and drowsiness. It usually happens gradually, mostly in elderly people. A sodium level should be checked for people who exhibit these symptoms.
Side effects often go away within the first few weeks of treatment. However, some side effects tend to remain for the duration of the medication treatment. Side effects should stop when the medication is stopped. Because of these concerns, adolescents may best be treated with psychotherapy alone for mild to moderate depression. A minor who starts an antidepressant should meet with his or her health provider at least weekly during the first month of treatment, then every 2 weeks for the next few months.
Many medications are metabolized, or broken down, in the liver, by a system of enzymes called cytochromes, or CYP. Otherwise, the medications would stay in the body until they reached dangerous levels. After being broken down by the liver, the medicines are sent to the kidneys, where they leave the body in urine. Many antidepressants are metabolized by the CYP 2D6 system. Some also inhibit the 2D6 enzymes-they slow down the metabolism of other
medications. The levels of the other medications become higher than expected. Doctors and pharmacists need to keep track of this so they can avoid drug interactions. The antidepressants fluoxetine, paroxetine, and bupropion are strong inhibitors of CYP 2D6 and can raise the levels of many other medications. People taking them should avoid over-the-counter cough medicines containing dextromethorphan, which is metabolized by 2D6. These antidepressants can also increase levels of the Tricyclic antidepressants. Since high levels of TCA’s can cause heart conduction delays, the combination of an SSRI and TCA must be carefully monitored by a physician. Sertraline is a weaker inhibitor the 2D6 system and is less likely to interact with other medications.
Some medications are metabolized by the CYP 3A4 system. This system is inhibited by grapefruit juice. This is why people are often told to avoid grapefruit juice when taking certain medications. Fluoxetine, sertraline, and nefazodone inhibit the 3A4 pathway. Fluovoxamine inhibits the CYP 1A2 pathway. This system breaks down caffeine, and flouvoxamine will intensify the side effects of caffeinated beverages (jitteriness, insomnia, heart palpitations).
Serotonin syndrome is a rare but potentially dangerous combination of excessive serotonin. This was traditionally seen with the oldest class of antidepressants, the MAOI inhibitors, when they were combined with certain medications. The syndrome consists of fever, rapid pulse, agitation, confusion, hypertension, nausea, sweating, diarrhea, incoordination, rigid muscles, and/or excessively strong reflexes. It can progress to coma and death if not treated promptly.
There have been reports of serotonin syndrome with combinations of medications or recreational drugs that increase serotonin.
Stimulants such as Ritalin (methylphenidate) or Adderall (amphetamine/dextroamphetamine) have gotten a lot controversy. These are commonly used to treat Attention Deficit Hyperactivity Disorder or narcolepsy (a neurological condition of excessive sleepiness). They are sometimes used in combination with other medications to help them work better or to combat fatigue.
Many parents express concern about “medicating” their children by putting them on stimulants for ADHD. They have a perception that the schools want to “drug” their children and turn them into “zombies” by keeping them quiet and taking away their personalities so that they don’t cause problems for the school. This is a very unfortunate stereotype that does a grave disservice to the children who most need help. ADHD is a neurological condition in which the prefrontal cortex, the part of the brain that controls attention, impulse control, learning and memory, is less active than normal. ADHD can be helped with medication just like any other medical condition. When the stimulants are doing their job, they are correcting the problems in the prefrontal cortex so that the child can pay attention, learn, and socialize. The “zombie” effect is the result of overmedication. Stimulant dosages tend to have a “window” in which they work optimally. Too little, and they’re only helping a little; too much, and the child will have side effects, such as appearing to “zone out” even more than usual.
Sadly, it is often parents that are least informed on medications that tend to have the most concerns about stimulants and be the least likely to allow their children to try them. (particularly Ritalin, which is no more harmful than any of the other stimulants, but tends to be more notorious). They have the least access to scientific information, and so must rely on rumors and anecdotes. The parents from the highest, most educated socio-economic groups tend to have the least hesitation about their children taking ADHD medication. They want their children to do well in school and be accepted into good colleges. This unfortunately perpetuates the gap between privileged and non-privileged groups.
Stimulants have received a lot of negative press in the past 30 years. There have been sensationalized cases in which a young people committed violent crimes while taking stimulants. At their trials, the defense teams argued that it was the stimulants that caused them to commit crimes. Of course, the likely explanation was that the people committed the crimes because of underlying aggressive tendencies, which stimulants unfortunately failed to improve. In fact, some very good studies have shown that stimulants tends to improve aggressive behavior, even in young people who don’t have ADHD (Klien, RG, Archives of General Psychiatry, 1997).
There were some lawsuits in the 1970’s alleging that Ritalin (methylphenidate) caused tic disorders (abnormal twitches of the face or upper body) in children. We know that stimulants can bring out tics in children who have a tendency to tics or a family history of tics (as many as 24 % of normal children will have temporary tics at some point of their growth that they might not even notice.)(Snider et al, 2002) There is no evidence that stimulants cause permanent, irreversible tics. Tics caused by a stimulant should stop when the stimulant is stopped.
A small percentage of children become more irritable and tearful when taking stimulants.
This can be countered by lowering the dose or changing to a different type of ADHD medication.
There has been concern on and off since the 1970’s that stimulants can stunt growth. We know for certain that they suppress appetite, and it can be difficult to for children to gain weight when they take them. (There are ways to work around this, such as adding calorie-rich foods like peanut butter and cheese.) We also know that children who are malnourished can fail to gain height. There have been several studies trying to clarify the effects of ADHD medications on growth. One study suggested that young teenagers with ADHD tended to be shorter than average regardless whether they took medication. This was felt to be due to a temporary effect of ADHD on growth, since no differences were seen in adults with or without ADHD (Spencer et al, 1996).
There have been recent results from the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder-abbreviated as MTA. This was a large study conducted by 18 ADHD experts at 6 different medical centers. Almost 600 elementary school children were treated and studied for 14 months. They were divided into 4 groups: 1) children treated with a stimulant (usually methylphenidate) monitored by an expert 2) children treated with behavioral therapy 3) children treated with a combination of 1) and 2), and 4) children treated with “community treatment as usual”-the treatment they would have received if they hadn’t been part of the study. (Group 4 usually received a stimulant from their local health professionals.) Results were first published in 1999, but the children were monitored for side effects for 24 months after the study ended.
In 2004, the MTA group released its findings on growth. They compared children who had received medication continuously for the previous 2 years with those who had never received medication. They found that the group who had never received medication had grown a little more (4.85 inches, or ½ inch above the national average) than the group who had received medication (4.1 inches, or ¼ inch below the national average.) They also gained more weight- 22 lbs. vs. 13.5 lbs. in the medicated group. The investigators recommended weighing the potential effects on growth against the potential problems associated with untreated ADHD, such as academic and relationship difficulties, juvenile delinquency, and substance abuse. They recommended that children taking ADHD medication have their height and weight monitored regularly.
In another study, 178 children receiving long-acting methylphenidate (Concerta) were only 1/10th of an inch shorter than average after 21 months on medication. Decreases in growth occurred mostly in the tallest children. Similarly, weight loss was most common in the children
who were overweight at the beginning of the study (Spencer et al, 2006). Children have continued to be followed since these studies; Later research showed that the growth spurt of puberty may have been delayed by six months but there has been no difference in average height or weight between adults who did or did not take stimulants as children. The latest data, collected in 2019, showed an approximate 1 inch difference in height between those treated continuously for 16 years vs. children without ADHD.
A study of Atomoxetine (Strattera, an ADHD treatment that works differently from a stimulant), found that height had dropped to 1.2 cm below expected when children were started on it before puberty but no difference if it was started during or after puberty.
Atomoxetine was given a “black box warning” in 2005 due to a 0.4% rate of suicidal thoughts early in treatment (5/1357) vs. none in the placebo group. One of the 5 attempted suicide but there were no completed suicides. A warning was added in December 2004 after 2 patients (out of 2 million people taking Atomoxetine) developed severe liver disease. (This reversed after Atomoxetine was stopped.) The manufacturer recommends monitoring for symptoms of liver damage (yellow eyes or skin, itching, abdominal pain, dark urine, flu-like symptoms.)
The blood pressure medications Clonidine or guanficine have also been shown to help ADHD.
Stimulants were in the news in 2005 after Adderall XR was temporarily taken off the market in Canada. There had been reports of sudden death in 12 minors who had taken it. 5 of them had pre-existing heart defects, and many of the others had other medical issues at the time of death. (Heat exhaustion, dehydration, near-drowning, heart attack, diabetes mellitus, drug overdose and excessive exercise were listed in the FDA’s 2005 public health advisory.) Per the FDA, the number of deaths did not appear to be different from the number of deaths that would have been expected been in this population regardless of medication use. A warning that Adderall products should be avoided by patients with underlying heart defects was added to Adderall XR’s labeling in 1994.
What was the cause of the deaths for the patients with heart defects? We don’t know for certain. We know that stimulants increase heart rate and blood pressure. A large increase in heart rate and blood pressure can be dangerous for people with weak hearts. They may have developed irregular heart rhythms that caused their hearts to stop.
Obviously, no patient wants to face the possibility of dying from a medication. Remember, the incidence of sudden death from stimulants is extremely small compared to the number of people taking them. There are ways to further minimize the risk. (These are not absolutely necessary. They are precautions for patients or families who are worried about this risk.)
Patients who wished to try stimulants could meet with a cardiologist (a heart doctor) for an examination. They could be tested with an echocardiogram, which measures the heart rhythm at a single point in time. An additional precaution would be a cardiac ultrasound, which can check for heart structure abnormalities. Those who are extremely cautious could wear a 24-hour holter monitor, which measures the heart rhythm for an entire day to catch any irregular rhythm that an EKG could miss. The combination of EKG, cardiac ultrasound, and holter monitor will catch virtually any possible heart condition. (Children will be reassured to know that these tests are painless- they are measured with monitors placed on the chest.) However, after extensive research, the current guidelines are that these tests may not be necessary if risk factors for heart disease are absent. These include having a family or personal history of a heart condition, having chest pain, getting easily winded with exercise, or having fainting spells.
There has also been concern over the use of atypical neuroleptics in minors. These are medications used to treat psychotic conditions such as schizophrenia- conditions in which one has a distorted view of reality, with delusions and/or hallucinations. These medications are therefore sometimes called anti-psychotic medications. They are also sometimes used for serious conditions in which functioning is significantly compromised, such as Bipolar Disorder or severe aggression. In low doses, they may be added to other medications to help them work better for some conditions, such as sever depression or obsessive compulsive disorder. A better name might be dopamine modulators, since they affect a brain chemical called dopamine.
They are called atypical to distinguish them from the older anti-psychotic medications. The older classic or first-generation medications have been used since the 1950’s. They are usually very effective in treating agitation, delusions, and hallucinations, but can have many side effects. A big problem with the neuroleptics has been their association with what extrapyramidal symptoms (abbreviated EPS, named after the part of the nervous system that is affected).
Extrapyramidal symptoms include tardive dyskinesia, dystonias, akathisia, and parkinsonism.
A person who used neuroleptics for years could develop a movement disorder called tardive dyskinesia. Tardive means late- these side effects can show up after long-term use, even after the medication has been stopped. Dyskinesia means movement problem. Tardive Dyskinesia is abnormal movements of the body, usually the face, tongue, lips, trunk, arms or legs. By definition, the soonest they occur after a few months of treatment, but they usually occur after years of use. (If they happen sooner, they’re called acute dyskinesias, which are usually reversible and easier to treat.) Approximately 5% per year of people who take first-generation neuroleptics develop tardive dyskinesia. About a third of people who take these medications lifelong will develop tardive dyskinesia. Risk factors include being female, elderly, having a mood disorder or mental retardation, and having experienced other EPS earlier in treatment.
These reactions are caused by a lack of dopamine in the movement center of the brain, and may not go away even after the medication is stopped. Treatment involves lowering or stopping the medication, if possible, or adding medication that may help counteract the effects.
Monitoring for tardive dyskinesia is recommended every 6 months for first generation neuroleptics and every 12 months for atypical neuroleptics. A popular questionnaire is the Abnormal Involuntary Movement Scale. A patient will be asked to make a series of movements, such as sticking out the tongue or walking across the room.
It is important to monitor for abnormal movements before starting neuroleptics. A small percentage of the population has abnormal movements even without medication, which could be mistaken for tardive dyskinesia. Often the affected person does not notice the movements, but they can look odd to others. (Because serotonin inhibits the production of dopamine, serotonin reuptake inhibiting antidepressants also lower dopamine. There have been rare reports of extrapyramidal symptoms, including tardive dyskinesia with them.)
Dystonias or dystonic reactions are painful, hardened muscle contractions, usually occurring within the first 2-5 days of treatment in approximately 2% of those treated with a first generation neuroleptic. They are more common in younger males. They usually involve the neck, eyes, tongue, or jaw. They are painful conditions but are rarely dangerous. They quickly improve with treatment with anticholinergic medication like Benadryl (diphenydramamine) or Cogentin (benztropine). (Sometimes, anticholinergic medication is as a precaution to prevent dystonias when classic neuroleptics are started.)
Many people who take first generation neuroleptics develop a type of restlessness called akathisia (from the Greek word meaning, “not to sit.”) This is a feeling of inner agitation.
Patients have difficulty sitting still and feel a need to walk around. Sometimes, doctor’s mistake this for agitation from the disease and increase the dose of neuroleptic, making the problem even worse. This condition is treated by lowering the dose or changing to a different medication. If the neuroleptic cannot be changed, medications such as beta-blockers or benzodiazepines are added to counteract the effect.
Pseudoparkinsonism is a side effect from neuroleptics that resembles Parkinson’s Disease. (Neuroleptics decrease dopamine, which mimics Parkinson’s Disease.) This results in tremor, slowed movement, stiff muscles, and limited facial expressions. Anticholinergic medication can also improve this side effect.
A rare but dangerous side effect of neuroleptics is Neuroleptic Malignant Syndrome. This occurs in less than 1% of patients taking first-generation neuroleptics, usually within the first two weeks of treatment. Symptoms include fever, rigid muscles, and confusion. This is a medical emergency requiring supportive care in an intensive care unit.
The atypical neuroleptics generated a lot of excitement when they first came on the market because they seemed to have fewer side effects and work better than the older medications. The first was Clozapine-the gold standard of the atypical neuroleptics. (Gold standard means that it is the medication proven to work the best and newer medications are compared to it.) It worked in a somewhat different way from the classic neuroleptics by more specifically targeting the areas of the brain involved in schizophrenia. Some schizophrenic patients who had not responded to other medications improved tremendously with Clozapine. The classic neuroleptics had improved positive symptoms of schizophrenia-hallucinations, delusions, and agitation. However, Clozapine also improved negative symptoms, such as inactivity, social withdrawal, and poor motivation, as well as suicidal behavior. It seemed to lower the risk of tardive dyskinesia.
Unfortunately, 1% of people who took Clozapine developed agranulocytosis, a dangerous condition in which the bone marrow stops producing white blood cells, putting patients at risk for infections. There have also been cases of heart problems caused by Clozapine, with a recommendation to monitor for symptoms such as chest pain, shortness of breath, rapid pulse, flu-like symptoms. Because of side effects, Clozapine is reserved for patients who have not improved with other medications. Frequent blood tests are required to monitor for agranulocytosis.
Several new atypical neuroleptics have been developed. These seem to have a low risk of tardive dyskinesia and agranulocytosis. They appear to improve positive and negative symptoms of schizophrenia. (possibly not as effectively as Clozapine). They are now used more commonly than the first-generation neuroleptics. Because they are easier to tolerate, they have been prescribed for children more than the classic neuroleptics. Although children with mental retardation tend to be very sensitive to medication side effects, they appear to tolerate the atypical neuroleptics.
However, atypical neuroleptics can cause rapid and excessive weight gain, high cholesterol, and diabetes mellitus. Younger people tend to gain the most weight- as much as 60 lbs. Over the course of several months of treatment. Weight gain usually tapers off after a few months, but the extra weight is generally not lost unless the patient participates in a diet and exercise program, or stops the medication. The atypical neuroleptics vary in their tendencies to cause weight gain.
Clozapine and olanzapine tends to cause the most weight gain, and aripiprazole, and ziprasodone, the least. Weight gain varies by individual-some people don’t gain any weight from these medications. If a person has lost a lot of weight due to psychotic thinking, weight gain might be a desired side effect.
The American Diabetic Association and American Psychiatric Association published guidelines for monitoring atypical neuroleptics in 2004. Recommendations include evaluation of personal and family history of risk factors for heart disease (obesity, high blood pressure, diabetes, heart disease) at baseline (prior to treatment), then once per year; weight for height calculations at baseline, then at weeks 4, 8, 12, 16, and annually; waist size at baseline, then annually; blood pressure at baseline, at 12 weeks, and annually; fasting blood sugar at baseline, 12 weeks, 16 weeks, and annually; and fasting cholesterol profile at baseline, 12 weeks, and annually (J Clin Psychiatry 2004). In addition, patients should be monitored for symptoms of high blood sugar-weakness associated with excessive drinking, eating, and urinating.
Many people receive education on healthy eating habits and begin a diet and exercise program at the same time they start atypical neuroleptics. This often prevents or slows down the weight gain. Sometimes medications are added to control weight gain- metformin, a medication used for Diabetes Mellitus, or topiramate, a medication used to prevent seizures.
Both first and second generation neuroleptics can cause increased production of prolactin. This is a hormone that is normally inhibited by dopamine. When dopamine levels go down, prolactin levels go up. Prolactin is required for lactation, the release of milk from the breast that occurs when a mother feeds her baby. It is normal for both women and men to produce prolactin in small amounts, but neuroleptics can increase this substantially and cause breast enlargement and milk production. This can interfere with menstruation in women and sexual function in men. There is a possible association between chronically elevated prolactin levels and a type of brain tumor.
To check for increased prolactin levels, physicians will question women about any menstrual irregularities and men about any sexual problems. If patients have noted these problems, the doctor will recommend a blood test to check prolactin level. The treatment for elevated prolactin is to change to another neuroleptic less likely to increase prolactin. If this isn’t possible, a medication that lowers prolactin can be added. Of the atypical neuroleptics, risperidone is the most likely to raise prolactin levels, and ariprazole and quetiapine, the least.
Other troublesome side effects can be sleepiness and difficulty concentrating. This can cause problems with learning. Generally, however, this is offset by the positive effects of the medication-the treatment of psychosis and/or agitation that allows the child to stay in school.
Mood stabilizers are medications that do just what their name implies- keep the mood stable. Psychiatrists use them mainly to treat Bipolar Disorder and aggression. They are sometimes used for other conditions, such as schizophrenia. Many are anti-seizure medications, which have been also shown to work for mood disorders. The theory is that the mood swings of bipolar disorder are like “emotional seizures.”
Lithium was the first medication found to work for Bipolar Disorder and continues to be the “gold standard.” Lithium is one of the few medications that have been shown to reduce the suicide rat. It has repeatedly shown to be effective for Bipolar Disorder. In smaller doses, it is used to help antidepressants work better. Lithium is a safe medication when taken and monitored as directed. However, the difference between an effective dose and a dangerous dose can be small. Lithium is dangerous in overdose. leading to nausea, vomiting, tremor, diarrhea, imbalance, stupor, coma, then death if untreated. Lithium level is monitored with frequent blood tests at the beginning of treatment and whenever a dose change is made. After dose has been stable, a lithium level is checked every 6 months.
Lithium is a naturally-occurring salt that dissolves in the bloodstream. The lithium level can increase when the body loses water by vomiting, diarrhea, or dehydration. Losing salt by sweating can also increase lithium levels.
Lithium leaves the system the same way water does-by urination. Needing to urinate more frequently is a common lithium side effect. This is associated with increased thirst. Lithium can damage the kidneys very rarely. Kidney function is monitored with blood tests every 6-12 months to insure that this is not occurring.
Lithium can be taken up by the thyroid gland, which controls metabolism. Thyroid function is normally checked with a blood test every 6 months. Over time, lithium can cause hypothyroidism, or low thyroid function. Untreated, this results in low metabolism- low energy, sleepiness, difficulty concentrating, weight gain. Patients who develop hypothyroidism can correct it by taking thyroid hormone in pill form.
Rarely, lithium can cause problems with heart conduction. An EKG prior to treatment is recommended for elderly patients or those with pre-existing heart problems. Other side effects include tremor, inattention, nausea, diarrhea, weight gain (although usually less than many other agents), and rash.
Pain relievers such as aspirin and ibuprofen can increase lithium levels. Acetaminophen is recommended when pain relief or fever control is needed unless lithium levels are carefully monitored.
We have a lot of information about the safety of antiepilepsy medications for children, since pediatric neurologists have used them to treat seizures for years. Medications that may be prescribed for Bipolar Disorder include valproate, carbamazepine, lamotrigine, and Topiramate. If these medications are discontinued, they should be slowly tapered if possible, since abruptly stopping them may increase the risk of having a seizure.
Common side effects of valproate, or Depakote, are weight gain, sedation, decreased concentration, abdominal upset, and tremor. Some people also experience hair loss. People who receive significant benefit from Valproate often remain on it even if they experience these symptoms.
Polycystic Ovarian Syndrome (PCOS) has been associated with the use of valproate in women and teenage girls. In one study, 40% of women taking valproate to control epilepsy had this syndrome, but it is unknown whether women with epilepsy are more prone to PCOS than women with Bipolar Disorder (T Betts, April 2001, Seizure). This is a condition characterized by excessive male hormone, obesity, ovarian cysts, menstrual irregularities, facial hair, weight gain, male-pattern baldness, acne, and/or diabetes mellitus. Women who experience irregular menstruation and teenage girls who have not gotten their periods as expected should have an endocrinology evaluation for this condition.
Some side effects, while quite rare, are dangerous enough to require immediately stopping valproate and receiving medical attention. Pancreatitis is a rare side effect that should be suspected in those experiencing upper abdominal pain, nausea, fever, and chills. Liver failure is a rare but potentially life-threatening complication. For this reason, patients and families are cautioned to watch for symptoms of hepatitis, such as jaundice, nausea, fatigue, and appetite loss. Valproate may also inhibit the production of platelets, a type of blood cell that prevents bleeding. Patients are warned to watch for excessive bruising and easy bleeding. Blood tests measuring liver and platelet functioning are normally measured every 6-12 months. Valproate levels should be checked with a blood test after each dose increase.
Carbamazepine can also very rarely cause liver problems. Its main side effects are sedation, nausea, and dizziness, rash, and decreased concentration. It may cause weight gain, usually less than valproate or lithium. It can rarely cause a dangerous rash. Its most dangerous (but thankfully) rare potential side effect is suppressing the bone marrow. It can stop the bone marrow from making blood cells, resulting in dangerous bleeding or infections. Patients should report bruising, easy bleeding, pale skin, sore throat, fever, and other symptoms of infection to their doctor. Carbamazepine can speed up the liver’s metabolism and therefore lower the dose of other medications, including birth control pills. At the beginning of treatment, blood levels should be checked frequently, since carbamazepine can speed up its own metabolism
Lamotrigine, or Lamictal, is also treatment for Bipolar Disorder. It has been shown to improve and prevent recurrences of bipolar depression in adults but has not been shown to help acute mania. It is also used to treat unipolar depression that has not responded to antidepressants. It tends to be better tolerated than the other mood stabilizers and does not require blood testing.
However, it is associated with a dangerous, painful rash called Stevens-Johnson syndrome.
This was found in 0.8% of children under 16 and 0.3% of adults who were taking it for seizures. This is less likely to occur when lamotrigine is started at a very low dose and increased very slowly. Patients who develop a rash need to speak to their doctor right away, particularly if they also have hives, fever, swollen lymph glands, lips, or tongue, or painful sores in the mouth or around the eyes. Lamotrigine must be increased even more slowly if it is used with valproate, which raises lamotrigine blood levels. Birth control pills lower lamotrigine blood levels and lamotrigine lowers the effectiveness of the birth control pill.
Topirimate, or Topamax, is one of the few mood stabilizers to be associated with weight loss instead of weight gain. However, it has not been shown to be effective for Bipolar Disorder when used alone. It is sometimes used with mood stabilizers or atypical neuroleptics to prevent weight gain. However, it can be associated with sedation, dizziness, decreased concentration, and word- finding difficulties. Other potential side effects include kidney stones, decreased sweating, and increased body temperature. Side effects of particular concern are glaucoma and metabolic acidosis. Glaucoma is increased eye pressure that can result in blindness if not treated. Patients should contact their doctor if they develop eye pain or vision changes. Metabolic acidosis is increased blood acidity due to lowered bicarbonate levels. Doctors should be notified for associated symptoms of sleepiness, rapid breathing, or irregular pulse. Since mood stabilizers can be associated with birth defects, anyone who could potentially be pregnant should have a pregnancy test before starting one.
Why risk taking these medications at all? The risk of treating a condition must be weighed against the risk of not treating. For people with significant depression or anxiety, potential side effects are a small price to pay for the relief the medication provides. Have you ever taken medicine for a bad headache? Aspirin can have side effects as well-possible upset stomach, bleeding problems, or ulcers. You must weigh the risk of side effects vs. the intense headache relief.
Several studies show that antidepressants can benefit minors. Fluoxetine, sertraline, and citalopram have been shown to improve depression. Fluoxetine, sertraline, citalopram, and fluvoxamine have had demonstrated effectiveness against anxiety disorders. In 2004, the suicide rate for children and teenagers rose for the first time in over 10 years. This corresponded to a 20% drop in antidepressant prescriptions for minors following the “black box warning.” A new study released in April 2007 found that the benefits of antidepressants for minors with anxiety or
depression clearly outweighed the risks. It analyzed information from 27 studies involving over 5000 patients ages 19 and younger. The risk of suicidal thoughts was found to be lower than that in the FDA analysis (Bridge et al).
What are the risks of not treating depression or anxiety? It is impossible to predict this for an individual, but research helps us to make some generalizations. The purpose of psychiatric treatment is to help keep children or teenagers on their growth track-functioning well in important areas such as friendships and school. Like running a race, once a child fall behind, it becomes increasingly harder to catch up to peers. Depressed or anxious children may have difficulty paying attention in class and fall increasingly behind in school. They may be irritable with other children, or withdraw and stop participating in activities, resulting in the loss of friendships.
We know that the body releases cortisol when under stress– a hormone that helps the body get moving in an emergency. There is evidence that excessive amounts of cortisol can damage parts of the brain, such as the hippocampus, an area that influences mood and certain types of memory. (Czeh et al., 2001). Stress also reduces the level of brain-derived neurotrophic factor, or BDNF, a protein that helps the brain’s nerves survive and grow (Smith et al., 1995, Castrén, 2004; Malberg et al., 2000).). (Antidepressants appear to improve nerve growth, particularly in the hippocampus (Castrén, 2004)). There is evidence that stress affects other parts of the body as well, decreasing our ability to fight illness. This makes it important to control stress. Depression has been associated with heart disease, asthma, and other medical conditions. There is also evidence that psychiatric conditions become harder to treat and more likely to recur the longer they are left untreated. For example, a person may first develop depression due to stress, such job loss or divorce. However, the depression may later take on “a life of its own” and return without any apparent outside trigger.
What are the risks of not treating a psychotic condition? These can be very serious. Psychotic people are out of touch with reality and can easily react impulsively and aggressively, feeling that the world is out to get them. The feelings associated with psychosis are very unpleasant- extreme anxiety and agitation. A psychotic person may be tormented by auditory hallucinations– one or more voices making frightening comments such as, “you’re worthless” or “kill yourself.” Sometimes, depression is accompanied by psychotic thinking that is not obvious to others.
Symptoms will improve much more rapidly with antipsychotic medication.
Schizophrenia is a debilitating psychotic condition that often begins during adolescence. There is evidence that treating it early with antipsychotic medication improves the course, and that the more treatment is delayed, the more serious the condition is and the harder to treat (Perkins et al., Am J Psychiatry 2005).
Neuroleptics can often help severe aggression and mood swings, without psychotic thinking. These medications should not be used for the normal moodiness that can accompany the teenage years, or the temper tantrums of young children. They are not appropriate for behavioral problems that can be treated by a therapist, who helps parents to set limits with children.
Neuroleptics should be reserved for agitation and moodiness that could be dangerous. Example include trying to jump out of moving cars, grabbing kitchen knives, and throwing heavy furniture. In these situations, neuroleptics can make the difference in allowing children to stay in school, learn, and make friends. Children who experience such intense mood swings describe them as horrible. They feel uncontrollable rage, and after the rage attack is over, they feel shame
and regret. Having medicine to help control their impulses gives them hope. They feel proud and happy that they can control their aggressive impulses and have improved friendships and grades.
Bipolar Disorder is a very disabling condition that prevents its sufferers from meeting their potential. When they are manic, they risk of acting impulsively, interfering with relationships and finances. When they are depressed, they have difficulty motivating and mobilizing themselves and may have suicidal thoughts. Despite its possible side effects, lithium is life- saving for many Bipolar patients. There is solid evidence in rigorous scientific studies that lithium prevents suicides in patients with unipolar and bipolar depression. Therefore, patients tend to continue lithium even if they develop side effects such as hypothyroidism, choosing to take thyroid replacement hormone rather than risk the return of severe mood swings.
After improving on a medication, my teenage patients often want to stop it prematurely. Why is this? As a teenager, it’s normal to try new things and test limits. Teenagers often want to do things differently from their parents. They may feel that they’re taking medication only because their parents want them to. Often, they want to fit in with their friends, and think that taking medication makes them “different.” Sometimes, their friends pressure them to stop taking medication, making comments such as, “Only crazy people take those kinds of pills.” Sometimes, teenagers find frightening Internet web sites in which people talk about horrible side effects they attribute to the medication. (I caution patients to trust only scientifically-oriented web sites. Some can be very biased- people who have bad reactions to medications are much more likely to report them on a web site than people who have had good reactions.) Teenagers may be experimenting with alcohol or recreational drugs that they know should not be combined with their medications. They may dislike the sexual side effects of their medications if they are becoming sexually active.
I try to avoid pressuring patients to start medication or stay on medication. I educate them on the risks vs. benefits and help them make an educated choice. I try to help teenagers set aside any conflict with their families that may be influencing their decision so that they can make an educated decision based on the facts and not on emotion.
Sometimes, teenagers abruptly stop taking their medication without telling an adult. If they have been taking a type of antidepressant called a serotonin reuptake inhibitor, they may have a discontinuation syndrome within the next 72 hours. They may experience a light-headed sensation, nausea, and/or headache. This is not physically dangerous, but can feel very unpleasant, like the flu. Patients sometimes mistakenly believe either that the syndrome is “proof” that they need to stay on the medications forever, or that the medications are so unpleasant that they never want to try them again. Neither response is based on fact. The discontinuation syndrome can be avoided by very gradually lowering the dose of medicine before stopping it. This should be supervised by a physician.
Many people object to taking medications because they don’t want to be “dependent” on “drugs.” Although medications are sometimes called “drugs,” they are different from the recreational drugs that are abused to “get high.” Although antidepressants improve mood, they don’t artificially elevate mood beyond normal when they are working correctly- they help the brain to function normally. (The exception is when a Bipolar person develops mania from an antidepressant.) People are no more dependent on antidepressants than they are dependent on insulin to treat their diabetes- they need the medication to treat the medical condition. Starting a medication does not mean that you will continue on it indefinitely. Ideally, a patient will learn psychotherapy techniques to prevent further episodes of depression or anxiety. The
recommendation is to stay on an antidepressant for approximately one year after symptoms have improved, then slowly lower the medication to see if it is still needed. (There are some medications that people may remain on for years, such as those for bipolar disorder or schizophrenia, which are often lifelong conditions.)
Patients normally don’t “crave” their antidepressant. They don’t go from doctor to doctor trying to obtain more of it or give up activities because of it. Antidepressants are not addictive.
Some medications are “controlled substances”-they are categorized as having addiction potential by the United States Drug Enforcement Administration (DEA). They have certain rules about how they can be prescribed. Categories range from II (high abuse potential), to V (low abuse potential). Antidepressants are felt to have no abuse potential are not classified as controlled substances.
Some psychiatric medications do have abuse potential. Stimulants are classified as category II controlled substances, although most people use them safely and do not become dependent on them. Long-term studies have shown that children with ADHD who are treated with stimulants are actually half as likely to abuse recreational drugs when they become teenagers and adults than those who were not treated (Wilens, Timothy, 2005).
A small percentage of people will become addicted to stimulants and should not be prescribed them. People most at risk are those who have a history of addiction to other substances. (People who have close family members with substance use problems should be prescribed stimulants cautiously, since substance dependence tends to run in families). This does not mean they are “weak” or “bad” people- the stimulants affect their brains in ways differently from most people. Vulnerable people get a feeling of artificial well-being from stimulants that most people don’t.
They find themselves becoming tolerant to its effects and craving more of it. They use more of it than intended and run out of it prematurely. They may make excuses to their doctors of why they need a new prescription early. There are safe non-addictive ADHD treatments for people who are at risk of stimulant dependence.
Benzodiazapines are another type of controlled substance sometimes used by psychiatrists.
They classified as category IV. Common names are lorazapam, or Ativan; alprazolam, or Xanax, diazepam, or Valium, and clonazapam, or Klonopin. Neurologists commonly use this class of medication to treat children with seizure disorders. Psychiatrists prescribe them for short-term treatment of anxiety or agitation. If benzodiazepines are used regularly (twice a day for long- acting forms; three or four times per day for shorter-acting forms) for more than a few months, they can cause physical dependence. If they are stopped abruptly, they can cause anxiety, jitteriness, nausea, sweating, and rarely, seizures. The dose should be decreased gradually, under the supervision of a physician. They are used more commonly for adults than for children, but can be helpful for some sleep disorders and when rapid alleviation of anxiety is needed.
The Treatment of Adolescents With Depression Study (TADS) provided important information on the outcomes for teenagers treated with psychotherapy and/or medication. This compared 439 patients with Major Depression between ages 12 to 17 who were assigned to either fluoxetine, cognitive behavioral therapy, a combination of both, or placebo. After 12 weeks of treatment, teenagers who were treated with the combination of fluoxetine and CBT improved the most. Those who took fluoxetine alone also improved. CBT alone was not significantly more effective than placebo except for young people from higher income families. About 30% of teenagers had significant suicidal thoughts before they began treatment, which greatly improved as treatment progressed. Teenagers who received combined treatment had the largest decrease. There was a slightly increased risk of suicidality in patients receiving fluoxetine alone compared to those receiving CBT. This was not seen in those receiving combined treatment, and it was speculated that CBT protects against suicidal ideation in patients given fluoxetine. (March et al., Journal of the American Academy of Child and Adolescent Psychiatry, Dec. 2006)
Another study found that citalopram reduced symptoms of depression in 178 children and teenagers. There were no serious side effects. (Wagner, KD et al, American Journal of Psychiatry, June 2004) Two studies found that sertraline improved major depression in children and adolescents. (Wagner, KD et al., JAMA 2003) Another study found that paroxetine improved major depression in adolescents (Keller, MB, et al., J. American Academy of Child and Adolescent Psychiatry 2001). A study of escitalopram found that it improved depression for adolescents (ages 12-17) but not for children (ages 6-11) (Wagner, KD, J. American Academy of Child and Adolescent Psychiatry, March 2006).