Antihypertensives

Clonidine and guanfacine, marketed as Catapres and Tenex, respectively, were originally developed as medications to reduce high blood pressure. They have been found helpful for reducing excessive hyperactivity and impulsivity in children with ADHD, but there is currently no evidence that these agents improve the cognitive impairments of ADHD. The effects for clonidine usually persist for about six hours, while guanfacine usually lasts a bit longer. Usual daily doses reported by the group led by Wilens (2002) are 0.05 to 0.4 mg for clonidine and 0.5 mg to 3 mg for guanfacine. Many physicians using these medications do a baseline ECG and monitor the patient's vital signs during treatment. The most common side effect of these antihypertensives is drowsiness, although they can also cause depression or rebound hypertension as they wear off.

The sedating properties of clonidine have been exploited to help alleviate the chronic difficulties in falling asleep that are common in many children with ADHD. Jefferson Prince and colleagues (1996) reported that of sixty-two children and adolescents treated with clonidine about an hour before bedtime, 85 percent had significantly less difficulty falling asleep. Many of these children (68 percent) were being treated successfully with stimulant medications during the day and were given small doses of clonidine, typically either a half or full 0.1 mg tablet, about an hour before bedtime.

Combined Medications

Because many patients with ADHD suffer from one or more comorbid psychiatric disorders, one medication is often not sufficient to control their symptoms. For example, as described above, many patients whose ADHD symptoms respond well to treatment with stimulants throughout the day continue to have great difficulty falling asleep at night. A significant percentage of these patients experience much less insomnia when taking a small dose of clonidine about an hour before bedtime. Yet for most of these patients, clonidine is of little or no help in alleviating the cognitive impairments of ADD syndrome and also tends to be too sedating to take during the day. For such patients the combination of stimulant medication during the day and atomoxetine or clonidine at bedtime may provide much better alleviation of ADHD symptoms without significant adverse effects.

Similarly, as discussed in Chapter 8, many individuals suffer from severe episodes of depression, crippling anxiety, or very burdensome obses sive compulsive disorder in addition to persistent ADHD. For these patients, concurrent treatment with a stimulant and a selective serotonin reuptake inhibitor (SSRI)—for example, fluoxetine, sertraline, paroxetine, fluvoxamine, or citaprolam (marketed, respectively, as Prozac, Zoloft, Paxil, Luvox, and Celexa)—or another such agent may alleviate both sets of symptoms in ways that no one medication alone could. Davis Gammon and I (1993) reported a study in which fluoxetine was successfully administered with stimulants to children who had ADHD as well as depression and other symptoms. Recent findings about an increase in suicidal thoughts or behavior in a small percentage of children or adolescents taking SSRIs, however, has led the FDA to urge close monitoring of use of any anti-depressant prescribed for any purpose to children and adolescents.

Treatment with combinations of medications for ADHD and various comorbid disorders is now relatively common and apparently is becoming more widespread. Daniel Safer, Julie Zito, and Susan dosReis (2003) reported that in the mid-1990s more than 20 percent of youths in outpatient psychiatric treatment and 40 percent of those receiving inpatient psychiatric care were given two or more concurrent psychiatric medications. Their findings indicate that the frequency of such combined treatment is becoming increasingly common, especially for youths being treated with stimulants for ADHD. This is not so different from other fields of medicine; combined medication treatments have been shown to be significantly more effective than single medication treatment for HIV, intractable seizures, congestive heart failure, and hypertension.

The problem of combined medication treatments in psychiatry, especially when used for the treatment of children, is that the effects of medicines given for psychiatric disorders are more difficult to measure than those used to treat many medical problems for which critical levels of antibodies, blood pressure, seizure activity, coronary output, and other vital readings can be easily ascertained. Another important problem is that very little research has been done to assess the risks and benefits of treatment with these various combinations of medications.

There are a few published examples of such research, however. In addition to the studies by Prince and others (1996) and Gammon and Brown

(1993) cited earlier, Gabrielle Carlson and colleagues (1992) have reported on the combined use of MPH and lithium for children with bipolar disorder and ADHD. More recently Russell Scheffer and others (2005) reported a controlled trial of mixed amphetamine salts in combination with a mood-stabilizing medication in bipolar children whose ADHD was impairing even after their mood problems had been stabilized. And Bieder-man and colleagues (2000) reviewed the use of mood-stabilizing medications, antidepressants, and stimulants. The Tourette's Syndrome Study Group (2002) and Hazell and Stuart (2003) reported positive results using clonidine and stimulants in combination. And Michael Aman and colleagues (2004) summarized two studies on the combined use of stimulants and risperidone for disruptive behavior disorders. Since some of these were chart reviews or relatively small, open-label studies, there are limitations to what conclusions can validly be drawn; such findings are more suggestive than definitive.

Some are quick to criticize clinicians who employ combined medication strategies for treatment of ADHD and various comorbid disorders since there is so little research evidence to guide such treatments. While there is good reason to prefer treating patients with just one medication in accordance with guidelines supported by extensive clinical trials, in some cases combining medications may relieve substantial suffering while incurring what seems to be a relatively small risk.

Is it preferable to treat a child only with a stimulant that improves his severe problems with inattention and impulsivity, but does not aid his chronic, severe insomnia? Should a clinician treat an adolescent with severe bipolar mood swings only with a mood stabilizer and leave untreated the student's ADD syndrome impairments, which make it impossible for him to do his schoolwork even minimally well? Faced with such dilemmas, many clinicians, in consultation with the patient and family, choose to prescribe combined medication treatments for ADHD and comorbid disorders, despite the lack of sufficient research to guide the process. In such situations the apparent risks of not providing the combined treatments may appear to outweigh considerably the uncertain risks of providing such treatment while monitoring carefully for possible adverse effects.

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