Although the U.S. Food and Drug Administration has never approved a drug for the treatment of autism or PDDs, most of the medical treatments currently available for PDDs are drugs. Drugs are prescribed to address specific PDD symptoms, such as difficulty in focusing, hyperactivity, self-abusive behavior, depression, anxiety, and uncontrollable aggression. This section discusses the major types of drugs currently used, and explains why they work for at least some people with PDDs.

• Antidepressants
  
• Anti-anxiety drugs
  
• Antispasmodic medications
  
• Stimulants
  
• Neuroleptics
  
• Other medications

Sometimes medications that have not been formally approved by government regulators are available under "compassionate use" laws, including medications that normally would be available overseas. These rarely apply to PDDs. Some unapproved drugs may be made available to participants in human research trials. It is sometimes possible--if not absolutely legal--for a physician in one country to prescribe a medication available only overseas, and for patients to then have the prescription filled at an overseas pharmacy.

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Note for non-U.S. readers: Most of the brand names provided in this article are those used in the U.S. Brand names and formulations may vary in other countries, and some drugs may not be available elsewhere. Conversely, there may be new medications approved for use in Asia or Europe that have not made it to North America yet. If you're curious about an unfamiliar medication, look it up by its generic name to find the names of non-U.S. equivalents, or ask your doctor whether something similar is available where you live.

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You might wonder why medications have not been created specifically for autistic symptoms. Truthfully, with the past decade's explosion of drugs that work on the neurotransmitter system, researchers have barely completed preliminary research on medicines already discovered that might help people with PDDs. "Investigation is still warranted into the drugs that we do have available to see in which clinical population drugs are going to be effective," says Dr. Potenza. "There have been significant advances in regards to our abilities to target specific symptoms," he added, but more research is needed. It's likely that the next decade will bring psychiatric medications that target specific neurotransmitters more precisely, improving the quality of medical treatment nd reducing side effects.

Antidepressants

Today's antidepressants are much more advanced than those used just a decade ago, but they're still a blunt instrument for attacking brain dysfunction. There are several different types, and within each group related medications may function quite differently. That's why you shouldn't write off a whole family of drugs just because one was a disaster. A slightly different medication may turn out to be infinitely preferable.

All of the antidepressants should be used with care. Check package inserts and pharmacy information sheets to avoid interactions with other medications. Be sure to tell your doctor about any over-the-counter drugs you use, even aspirin, herbal medicines, or supplements.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Five drugs are currently considered to be part of the SSRI family:

• fluoxetine (Prozac)
  
• fluvoxamine (Luvox)
  
• paroxetine (Paxil)
  
• sertraline (Zoloft)
  
• citalopram (Celexa)

Each SSRI has major or minor side effects of its own--for adults, sexual dysfunction is often the greatest concern.

There are two serious side effects you should be aware of when starting to use SSRIs, or increasing SSRI dosage. First, SSRIs can trigger manic episodes in some people with bipolar disorder ("manic depression"). Manic episodes may be characterized by non-stop talking ("pressured speech"); grandiose thoughts, speech, and actions; paranoia; lack of need for sleep; flight of ideas; uncharacteristically risky behavior; and hyperactive movements. This effect is most often seen when SSRIs are used to treat depression in a person who actually has bipolar disorder rather than simple, unipolar depression. An acute manic episode can be dangerous to the patient's health, not because of any physical effect but due to the impulsive, extreme behavior that may occur during the episode.

Second, people who use SSRIs in overly high doses--or mix them with other medications that potentiate (increase) their effects, including herbal remedies like St. John's Wort--run the risk of serotonin syndrome. When the brain has too much serotonin, patients may experience shivers, headaches, diarrhea, profuse sweating, confusion, and a "jumpy" feeling that's intensely uncomfortable. If this happens, stop taking the SSRI immediately and see your doctor without delay. In extreme cases, serotonin syndrome can be fatal, although no fatalities have yet been reported from the combination of an SSRI and St. John's Wort.

Tricyclic antidepressants

• amitriptyline (Elavil)
  
• amitriptyline/perphenazine (Etrafon, Triavil)
  
• amitriptyline/chlordiazepoxide (Limbitrol)
  
• amoxapine (Asendin)
  
• clomipramine (Anafranil)
  
• desipramine (Norpramin)
  
• doxepin (Sinequan)
  
• imipramine (Tofranil)
  
• nortriptyline (Avenytl, Pamelor)
  
• protriptyline (Vivactil)
  
• trimipramine (Surmontil)

The tricyclic antidepressants work by inhibiting the uptake of various neurotransmitters at adrenergic nerve terminals, resulting in an increase of monoamine neurotransmission.

These drugs require regular monitoring for heart problems and other potentially serious side effects. They can lower the seizure threshold. As with the SSRIs, there is a danger of sending people with bipolar disorder into a manic phase. Some patients also complain of excessive weight gain.

Two serious side effects are associated with some tricyclics. The first is neuroleptic malignant syndrome (NMS). This potentially fatal condition is characterized by rigid muscle movements, fever, irregular pulse and heartbeat, rapid heartbeat, irregular blood pressure, heavy sweating, and strange states of mind. Discontinue the medication immediately and call your doctor if these symptoms occur. In extreme cases, the patient may need emergency care at a hospital. Physicians should report episodes of NMS to the Neuroleptic Malignant Syndrome Information Service, which has set up a registry to help researchers reduce the incidence of this problem.

Tricyclics may also carry a risk of Tardive Dyskinesia, an irreversible muscle movement disorder more usually associated with long-term use of the older neuroleptic drugs, such as Haldol. Between 20 percent and 30 percent of long-term neuroleptic users eventually develop this disorder, which is characterized by twisting motions of the hands and feet, and smacking or chewing movements of the mouth. It is hoped that some new medications may help patients prevent or treat this permanent side-effect. Some physicians recommend that people who take drugs that carry a risk for TD also take Vitamin E supplements, which appear to stave off the disorder in some people.

MAO Inhibitors

• moclobemide (Aurorex)
  
• phenelzine (Nardil)
  
• tranylcypromine sulfate (Parnate)

If you or someone you care for is taking a MAOI, check for warning labels on everything, and familiarize yourself thoroughly with the dietary restrictions.

MAOIs can also produce hallucinations, and have been abused by some drug users to get this effect.

Buproprion

Lithium

Lithium users need to have blood tests at regular intervals to monitor heart and kidney function, and to make sure the dose is at a therapeutic level. When this drug is taken with a neuroleptic, doses and side effects must be watched very carefully. There is a danger of encephalopathic syndrome with this combination. Encephalopathic syndrome's symptoms mimic those of neuroleptic malignant syndrome, of which it may be a variant. Lithium can be toxic in doses that are not much higher than the therapeutic dose. Despite these cautions, for most patients who experience extreme mood swings, lithium is well-tolerated and provides relief.

Mirtazapine

Nefazodone

Reboxetine

Venlafaxine

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Note: The National Alliance for the Mentally Ill is one of the best resources for information on new drugs for neurological disorders. Its Web site, http://www.nami.org/, often has "reviews" of new drugs, and previews of medications that are undergoing clinical trials.

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"Natural" anti-depressants

Based on reported effects and clinical trials, St. John's Wort appears to combine aspects of the SSRIs and the MAOIs. For that reason, it should be taken with the same care and caution as these types of prescription drugs. There have been anecdotal reports of patients with manic episodes attributed to St. John's Wort, or (more rarely) with unpleasant food or medicine interactions like those that can occur when taking MAOIs. There have been documented instances of serotonin syndrome associated with St. John's Wort, generally when a patient taking a prescription antidepressant "supplemented" it with this herbal remedy. Recent reports implicate this herb in temporary nerve damage, which can occur if the patient stays in the sun too long. Melatonin, a supplement used to regulate sleep, may also affect serotonin. Be sure to tell your doctor about any supplements, herbal medications, or folk remedies you add to your medication regimen.

Perhaps one of the most important natural anti-depressants is sleep. Researchers speculate that at least some of the positive effects attributed to anti-depressants are actually due to their sleep-inducing powers. Lack of adequate sleep is a powerful depressant, and sleep disturbances are often the first sign of impending depression. People with PDDs frequently have unusual sleep schedules, sleep disturbances, or full-fledged sleep disorders. Medications, exercise, relaxation techniques, and scheduling adjustments can help you get control over these problems. Proper sleep can make a huge difference, and it's best if you can achieve it without drugs.

Daily activities can be powerful mood-enhancers as well, from eating a healthful diet to cultivating interests that occupy the troubled mind. Scheduling, even right down to fifteen-minute blocks, can provide daily motivation and the reward of purposeful activity. This is precisely the approach to depression used by the best institutions for the mentally ill, in concert with medication and "talk therapy." You can take these preemptive steps to keep your general physical and mental health in balance, and they may enhance your immune system functions as well.

I think that you should try to find things that are fun for you, like work and school, a class that you really look forward to. That will help you, because you'll have a reason to go to sleep at bedtime. And eat breakfast, it really helps! --KayCee, age 16 (diagnosed OCD and bipolar disorder)

Anti-anxiety drugs

• alprazolam (Xanax)
  
• chlordiazepoxide (Librium)
  
• clonazepam (Klonopin)
  
• clorazepate (Tranxene)
  
• diazepam (Valium)
  
• lorazepam (Ativan)
  
• oxazepam (Serax)
  
• prazepam (Centrax)

Buspirone (BuSpar) is a non-benzodiazepine anti-anxiety drug and tranquilizer. Because it doesn't carry the addiction risk of a benzodiazepine, it may be preferable for some people. Four small studies have shown that BuSpar may be useful for reducing aggressive behavior, hyperactivity, and stereotypic movements in people with autistic symptoms. However, anecdotal reports indicate that some patients find this medication difficult to tolerate.

Buspirone is available as a transdermal patch as well as a pill. The patch has been tested for use in children, and was found to address hyperactivity in some with less of a "rebound effect" than amphetamines like Ritalin.

Sometimes BuSpar is added to an SSRI to prolong its effectiveness.

Antispasmodic medications

Kyle was on Depakote for seizure control [from] ages five to seven. This controlled seizures. One seizure, in which he was non-responsive for twenty or thirty seconds, caused our son to lose all expressive language for a week. Other symptoms of minor seizures included rapid eye movements back and forth for two to four seconds, followed by laughter or crying. These were controlled by Depakote, which may have helped preserve gains made by taking Prednisone. --Joe, father of seven-year-old Kyle (diagnosed PDD-NOS with autistic features)

• carmazepine (Tegretol)
  
• clonazepam (Klonopin)
  
• ethosuximide (Zarontin)
  
• ethotoin (Peganone)
  
• fosphenytoin (Cerebyx)
  
• gabapentin (Neurontin)
  
• lamotrigine (Lamictal)
  
• mephenytoin (Mesantoin)
  
• phenobarbital (Luminol, Solfoton)
  
• phenytoin (Dilantin)
  
• primidone (Mysoline)
  
• toiramate (Topamax)
  
• valproic acid (Depakene) and
  
• divalproex sodium (Depakote, Depakote Sprinkles)

Phenobarbital can be addictive, and at too-high doses can produce an effect that looks like alcohol intoxication. For these reasons, it is rarely used anymore, except in low doses or as part of a combination that includes a newer antispasmodic.

Antispasmodics are often prescribed in combinations, as two can be more effective together than one. However, mixing drugs can increase the risk of side effects. Monotherapy (treatment with a single drug) is believed to be the best choice whenever possible.

Some forms of epilepsy may also be treated with a combination of steroids, such as Prednisone, and antispasmodics. Steroids tend to cause weight gain and mood swings, and they suppress the immune system. Unless nothing else works, steroids should be avoided.

Gabapentin (Neurontin)

Other ways to address seizures

Some people with seizure disorders have reported beneficial effects from special diets and supplements, particularly from vitamin B6, and the supplements lecithin and DMG. These claims have been partially substantiated in small studies. One intervention that can definitely help in extreme cases is the ketogenic diet. This high-fat, low-protein, low-carbohydrate regimen has proved very useful for some young children with epilepsy, although it's a less than pleasant experience for the patient and should never be undertaken without medical supervision.

In a very few cases, seizure disorders cannot be controlled with medication, diet, or other efforts. Surgery may be considered. A new procedure involves implanting a small device called a vagus nerve stimulator in the chest.

People with uncontrolled epilepsy must take steps to prevent harm during a seizure. They may need to wear a helmet, change their surroundings, or avoid driving a car.

Antispasmodic drugs for aggression or SIB

Stimulants

Stimulants are the drugs most frequently prescribed to children with PDDs, despite the fact that no studies of stimulant use have been done in this population. In fact, the Autism Research Institute's database indicates that many autistic-spectrum patients have bad reactions to stimulants, including increased hyperactivity, aggression, and stereotypic behaviors or tics. Out of 2,788 families who replied to a survey question about Ritalin, 45 percent reported that it made their autistic children's behavior much worse.

Some researchers believe that stimulant use can cause brain damage. Certainly this is sometimes the case with illegal amphetamines. Ritalin has been in use for ADHD for quite some time now, but there still isn't much information available on the effects of long-term use.

Stimulants may be appropriate for some people with PDDs, however. If you choose to try them, start with a small dose and titrate very slowly for the best effect.

Miles has been on Ritalin since the age of five. It has enabled him to learn in a classroom environment, and to reduce the incidence of unsafe behaviors. We tried Dexedrine for about three months, it depressed Miles' mood significantly. --Amy, mother of seven-year-old Miles (diagnosed PDD-NOS and ADHD)

Stimulants that may be prescribed for symptoms of PDDs include:

• dextroamphetimine sulfate (Das, Dexampex, Dexedrine, Dexedrine Spansules, Dextrostat, Ferndex, Oxydess)
  
• dextroamphetimine/amphetamine (Adderall)
  
• methamphetamine (MTH)
  
• methylphenidate hydrochloride (Ritalin)
  
• pemoline (Cyclert)

The rebound effect can be rather nasty, but it's easily solved with careful dosing. Ritalin is the shortest-acting stimulant, and therefore the one with which the greatest amount of rebound trouble occurs. Doctors often ask that it be given at two-and-a-half to three-hour intervals, with half of a regular dose at bedtime to permit better sleep. A sustained-release version of Ritalin (Ritalin SR) is available, but gets low marks from patients when used alone. Dexedrine has a longer life (four to six hours), and the Dexedrine Spansule formulation can maintain its beneficial effects for up to eight hours.

Adderall is not as well-known as Ritalin, but it may be a better choice for many patients. It time-releases different amphetamine compounds smoothly over several hours, resulting in less chance of rebound.

Cyclert has a long action period, but is rarely used unless all of the others have failed to have positive effects. Regular liver monitoring is a must with this drug.

Stimulants and tic disorders

It is possible that stimulants cause tics to appear sooner than they would have otherwise, or that they make tics worse. Many people with Tourette's syndrome avoid stimulants because they have found this to be the case for them.

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Note to non-U.S. readers: Stimulants are not used as widely in Europe as they are in the U.S. for conditions other than narcolepsy. Patients in the U.K. and France may experience particular difficulty in obtaining any prescription medication for hyperactivity, regardless of how severe the problem is. Persistence--and seeking out a doctor who specializes in treating ADD/ADHD or who has experience in using stimulants with PDD patients--seems to be the key.

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Stimulants and addiction

Dr. Maria A. Pugliese, a Board-Certified Psychiatrist with added qualifications in Addiction Psychiatry at Pennsylvania Hospital and the Malvern Institute, says their fears are largely unfounded. "The biggest risk of addiction in children with ADD/ADHD comes from their genetic inheritance, not from their exposure to stimulant medication," says Dr. Pugliese. "There is a large crossover between families with ADD/ADHD and families with addictive disorders."

The greatest danger of prescription stimulant abuse occurs in junior high, when friends, siblings, or even parents may poach the patient's pills to get an illicit high.

"There are many safeguards built into the system to protect the public from stimulant abuse," Dr. Pugliese notes. "All stimulants except Cyclert are Schedule II drugs, meaning they must be written prescriptions, not phone-ins; they must be filled within seventy-two hours of being written, and there are no refills allowed without a new prescription. There are no indications that the stimulants that are prescribed for children with ADD/ADHD are addictive by themselves in therapeutic doses."

Parents need to make sure that proper safeguards are in place when medications are stored at home and at school. There have been many cases of theft or accidental use, sometimes with tragic results.

As for the fear that kids given stimulants or other psychiatric medications will come to think pills are the answer to all ills, says Dr. Pugliese, education is the answer--and it works. "Children come to learn quite early the difference between medications and 'drugs', because of schools' drug education and awareness programs," she says. "By the end of elementary school they are able to say the medication is 'good' and 'helps you get better', and that 'drugs' are 'bad for you' and 'make your life sad'." In addition, she notes, "if they have a serious psychiatric illness, they are much less likely to develop an addiction problem as an adult if their psychiatric illness is well-treated in childhood."

Over-the-counter stimulants

Side effects reported include high blood pressure, nausea, restlessness, anxiety, insomnia, irritability, and hallucinations. There have been cases of death, generally due to heart attack, from OTC stimulants based on PPA, ephedrine (or the herb Ephedra, also called Ma Huang, from which it is made), or even caffeine. If you insist on using these stimulants, tell your doctor, and monitor side-effects carefully.

Neuroleptics

The very first neuroleptics were discovered in the 1950s and 1960s, and represented the first major breakthrough in medical treatment for mental illness. However, the excitement was short-lived when the results of long-term use and verdose were discovered. Many of these older medications are still prescribed for people with PDDs today, however. They include:

• chlorpromazine (Thorazine)
  
• diphenylbutylpiperdine (Pimozide or Orap)
  
• fluphenazine (Prolixin, Prolixin Decanoate)
  
• haloperidol (Haldol, Haldol Decanoate)
  
• loxapine (Loxitane)
  
• mesoridazine (Serentil)
  
• molindone (Moban)
  
• perphenazine (Trilafon)
  
• prochlorperazine (Compazine)
  
• thioridazine (Mellaril)
  
• thiothixene (Navane)
  
• trifluoperazine (Stelazine)
  
• triflupromazine (Vesprin)

People involved in the care of institutionalized patients have noted that the older neuroleptics are used more often in these settings than one might think, possibly as a way to control patients in understaffed or poorly run facilities. Psychiatric nurses derisively refer to this approach as "using a chemical straightjacket." If you care for an institutionalized person, the potential for misuse or overuse of neuroleptics is something you should be on the lookout for.

The so-called atypical neuroleptics are recent discoveries. They blend functionality against schizophrenia, psychosis, self-injurious behavior, painful ticcing, and other major mental-health symptoms with far fewer side effects and dangers than their ancestors. Patients currently taking older neuroleptics should definitely ask their physician about making a switch. The atypical neuroleptic family includes:

• clozapine (Clozaril)
  
• olanzapine (Zyprexa)
  
• risperidone (Risperdal)
  
• quetiapine (Seroquel)
  
• ziprasidone (Zeldox)

Side effects to watch out for with all neuroleptic drugs include agranulocytosis (a dramatic drop in white blood cell count), Neuroleptic Malignant Syndrome and Tardive Dyskinesia, and withdrawal dyskinesias (temporary episodes with symptoms similar to Tardive Dyskinesia, which occur when the medication is stopped).

Neuroleptics may also cause extrapyramidal side effects (EPS). Physical symptoms include tremor, slurred speech, akathesia (an intensely uncomfortable itchy, jumpy sensation that may make the patient move around incessantly), and dystonia (uncontrollable muscle contractions). Emotional symptoms include anxiety, distress, paranoia, and bradyphrenia (slow thought processes).These are serious problems, the kind that understandably make patients want to stop taking their medicine. Careful medication choice and dosage adjustment should reduce these problems, and complimentary adjustments to diet, vitamins, supplements, and relaxation techniques may also help.

Excessive weight gain is also a common problem with both older and atypical neuroleptics.

Other medications

Anti-hypertension medications

• catapres (Clonadine)
  
• guanfacine (Tenex)

Clonadine or Tenex are often used to curb hyperactivity when stimulants don't work, or can't be combined with other medications. Both may also help curb aggression.

Clonadine is available in pill or patch form, although only the pill is available as a less-expensive generic. Patients generally prefer the patch. It's easier to use, and pill users tend to experience sleepy "crashes" as the medication is first absorbed in the bloodstream. The crash effect can interfere with school or work.

The Clonadine pill was definitely a wash. Our son was out like a light by ten a.m., and napped for well over an hour. We saw great improvements in his ability to pay attention, stay on task in class, and clamp down on his own inappropriate, impulsive behavior, but we had to go to the patch instead so he wouldn't sleep through first grade. The patch tends to fall off before it should, but it's a much smoother medication.

Both Clonadine and Tenex can affect heart function and blood pressure, so regular monitoring is a must. Neither medication can be stopped suddenly, due to the risk of a dangerous drop in blood pressure.

Opioid blockers

Nicotine