Basic psychopharmacology for children and adolescents revised (1)

Dr. Roy Q. SandersDirector, Child and Adolescent Psychiatry

Basic Psychopharmacologyfor Children and Adolescents

Basic Psychopharmacologyfor Children and Adolescents

Prescribing psychoactive medication for children is controversial. However, at times it is necessary to assist children in controlling problems with mood, behavior, anxiety, aggression and other difficulties. As a clinician I have to be convinced that to not medicate would be more harmful than to proceed with medication treatment.

Today we will discuss common reasons for prescribing medications and the specific medications prescribed for those problems.

Disorders of Concentration, Attention and Hyperactivity

One of the most common reasons psychoactive medication is prescribed in children is related to problems associated with disruptive behavior. In particular problems with concentration, and hyperactivity.

Choices of medications for these problems include

• Stimulants

• Strattera

• Alpha adrenergic agonist

• Some antidepressants

There are two basic types of stimulants

Methylphenidates

Amphetamines

Methylphenidate (Ritalin)

Methylphenidate (Ritalin) is one of the oldest of the stimulant medications used in the treatment of attention and concentration problems.

In general, methylphenidate is well tolerated and works well to increase concentration and attention and to decrease hyperactivity. It works about 80% of the time to reduce up to 80% of the symptoms a person is experiencing.

Methylphenidate (Ritalin)

Side effects include decreased appetite, decreased or disturbed sleep, sometimes headaches and gastrointestinal pains. At times motor or vocal tics emerge. There can also be problems with mood instability and with irritability. In overdose you can see psychotic symptoms or symptoms of delirium.

Methylphenidate (Ritalin) Problems can also arise with methylphenidate

because of the short half-life of the standard formulation. Theoretically dosing can occur every four hours but clinical experience leads to dosing as frequently as very 150 minutes. There are other forms of the medication that have longer duration of action including but not limited to Ritalin LA, Metadate CD, Concerta, Methylin and now Daytrana (a patch).

Dextromethylphenidate

• Focalin and FocalinXR both prescribed in similar fashion to other stimulants. Side effects are similar. The difference is perhaps in specificity.

Mixed Amphetamine SaltsAdderall and AdderallXR.

Mixed amphetamine salts have also been available in the treatment of attention and concentration for many years. They are currently available in generic and under the trade name of Adderall and AdderallXR.  

These medications are very effective in decreasing the symptoms of poor attention, poor concentration, and hyperactivity. Their effectiveness is similar to methylphenidate and they are very widely used.

Mixed Amphetamine SaltsAdderall and AdderallXR.

Side effects are also similar to those listed above with methylphenidate but in clinical experience they are slightly more likely to create some mood lability and irritability than the other stimulant medications.

A new amphetamine is Vyvanse a “pro-drug.”

Dextroamphetamine Dextroamphetamine has also been used for years

in the treatment of problems with attention, concentration and the regulation of activity level. Sold under the trade name of Dexedrine or Dexedrine Spanules.

Dextroamphetamine is effective in reduction of symptoms at a level consistent with the treatments listed above.

Side effects are similar to those listed above.

Other Medication Options for Attention, Concentration

and Over activity The mainstay of therapy for problems with

concentration and attention is stimulant medication. While stimulants are very effective medications there have been problems with their use because of the relatively short half life of each of these preparations. Even at their longest the medications rarely last greater than 8 hours and often times patients can experience a sort of rebound hyperactivity once the medication has “worn off”.

Atomoxitine (Strattera)

A noradrenergic reuptake inhibiter that appears to have relatively good effectiveness in decreasing levels of hyperactivity and in helping with increasing attention, concentration, and organization. It has been approved for use in children as young as 6 years old weighing above forty pounds. It generally has lasting effects throughout the day and into the evening. Problems have included changes in appetite and also nausea along with some sleep problems

Centrally acting alpha adrenergic agonist

Clonidine and guanfacine have also been very useful in decreasing levels of hyperactivity and in increasing attention and concentration. They are not necessarily as effective as stimulant medications but they are effective in a group of very aroused patients. Side effects are limited to problems with drowsiness and with hypotension.

Venflaxamine (Effexor) Venflaxamine (Effexor) a mixed serotonin and

noradrenergic reuptake inhibiter that has been used in the treatment of difficulties related to concentration, attention and regulation of activity level with some limited success. Recently, Venflaxamine has come under increasing scrutiny because of issues related to possible increased suicidal ideation and suicidal behaviors in children and adolescents taking serotonin reuptake inhibiters. Other problems have included increased irritability and possible increases in blood pressure.

Buproprion (Wellbutrin) Buproprion (Wellbutrin) is an anti-depressant

medication that is sometimes used in the treatment of problems with attention and concentration. Buproprion can be reasonably effective in the reduction of symptoms but must be used with caution in children or adolescents with history of seizures, head injury or bulimia. (This medication has also been included in the list of antidepressants where care as to be given secondary to fears of increased suicidal thoughts or behaviors.)

Tri-cyclic Antidepressants

Tri-cyclic antidepressants have also been used successfully in the treatment of problems with attention, concentration and regulation of activity levels. The tri-cyclics used in children most often include imipramine and nortrityline. They generally have good effectiveness over twenty four hours but they can have troublesome side effects that include a widening of the QRS as measured on EKG. Also they can lead to drowsiness, weight gain, dry mouth and constipation. It is also generally important to check serum levels of these medications while a child is being treated.

Anxiety

Anxiety disorders as a group are very common in children in general and are often misdiagnosed or overlooked if a thorough history is not obtained. Misdiagnosis can be of particular concern where medications are concerned. The wrong medication can serve to exacerbate symptoms associated with anxiety and lead to increased morbidity for the child.

Serotonin Reuptake Inhibitors Since their introduction in the last several years the serotonin reuptake

inhibitors have been the treatment of first choice in the treatment of anxiety. Fluoxetine (Prozac), sertraline (Zoloft), paroxitine (Paxil), citalopram (Celexa), escitalopram (Leapro), and fluvoxamine (Luvox). These medications taken as a whole have been very effective in reducing anxiety and also in decreasing anxiety related symptoms associated with perseveration and preoccupation. In general they should be used starting at low doses for most patients but especially with those diagnosed with pervasive developmental disorders. The medications should be gradually titrated to desired effect. Care should be given to look for the emergence of any agitation or irritability and these medications have been known to induce mania in predisposed patients. Also added care should be given to observe for any signs or symptoms associated with increased suicidal ideation or suicidal behaviors.        

Benzodiazepines Benzodiazepines as a class are excellent anti anxiety

medications. They can be very effective in the treatment of anxiety related problems in the developmentally disabled. These medications include but are not necessarily limited to diazepam, alprazolam, lorazepam, chlordiazepoxide, clonazepam, chlorazepate, oxazepam, flurazepam, and temazepam. Problems arise in these medications most often relate to somulence, difficulty with short term memory, development of tolerance requiring increasingly higher doses, and also with the half life and active metabolites of some of the medications in this class leading to unwanted prolonged effects.

Buspirone (Buspar)

Buspirone (Buspar) is an anxiolytic that can have some success in the treatment of anxiety. While not always successful in relieving anxiety it is a medication with very few side effects and is well tolerated. Generally, problems arise from needing to dose up to three times a day and it has a relatively slower onset of action sometimes taking up to three weeks to achieve clinically significant effect.

Venflaxamine (Effexor)

Venflaxamine (Effexor) is a combination serotonin reuptake inhibitor and noradrenergic reuptake inhibitor that has been clinically effective in decreasing anxiety symptoms. It has generally been well tolerated but there have been problems with sleep disturbance and even drowsiness on the medication. There have also been problems with elevations in blood pressure.

Tri-cyclic antidepressants Tri-cyclic antidepressants such as imipramine and

nortriptyline can also be effective anxiolytics. However, they may take up to 4 weeks to work effectively once an adequate serum level has been obtained. As when using in these medications in the treatment of other symptoms, care must be given to monitor the EKG to insure a QTc that is within acceptable clinical parameters. Also as stated above problems with high anticholinergic side effects can lead to problems like dry mouth, constipation, and drowsiness.

Antihistamines

There are times when anti-histamines such as hydroxyzine or diphenhydramine are prescribed to relief anxiety. While these medications may be effective in the short run sedating a patient and calming the “crisis” they are generally not good medications for long-term use in the treatment of ongoing anxiety symptoms.

Mood Problems

Depression and mood disorders certainly “exist” in children and often times psychotropic medications can be of assistance. More controversial currently is the diagnosis of Bipolar Disorder in a pediatric population. Great care is needed to ensure an accurate diagnosis so that appropriate treatment is given, especially when it comes to medications.

Depression The generally accepted first line of treatment for

depression is the choice of a selective serotonin uptake inhibitor.                                                                                                    

Serotonin Reuptake Inhibitors  These medications that were listed above include

fluoxetine (Prozac), sertraline (Zoloft), citralopram (Celexa), escitralopram (Lexapro), fluvoxamine (Luvox), and paroxetine (Paxil). All of these medications have generally the same level of effectiveness in the treatment of depression and choices are often made based upon side effect profiles or the past response to a particular medication by the patient or a close relative of the patient. These are generally considered safe and effective medications although their use in children has not been extensively studied.

Serotonin Reuptake Inhibitors 

Side effects in this class of medication are generally related to gastrointestinal problems, sometimes problems with sleep, and all generally tend to create problems with sexual function (in adults) that is usually related to decreased orgasm but there can also be decreased desire.

Serotonin Reuptake Inhibitors These medications can also cause problems with increased

irritability and at times they can induce mania in individuals with that predisposition. Care should be given especially when giving to individuals with a strong family history of Bipolar Disorder. Individuals with Pervasive

Developmental Disorders as well can be very susceptible to side effects of irritability and mood instability. These medications should be used at low doses and with appropriate caution. Care also should be given as mentioned above to issues associated with potential suicidal ideation and behavior.

Buproprion (Wellbutrin)

Buproprion (Wellbutrin) is effective in the treatment of depression and in general has been well tolerated. It has advantages over the other anti depressants used in adults in that it is generally accepted that it has fewer sexual side effects. This medication has also appeared to be less likely to create difficulties with inducing mania in individuals that may be vulnerable.

Buproprion (Wellbutrin)

Buproprion must be used in caution with individuals that have a history of head injury or those with seizure disorder or history of bulimia. These individuals may be at higher risk for seizure on this medication. Newer formulations of buproprion have lengthened the half-life of the medication and this has led to less risk of seizure in individuals. It still should not be given to individuals with the risk factors noted above.

Venflaxamine (Effexor)

Venflaxamine (Effexor) is a combination selective serotonin reuptake inhibitor and noradrenergic reuptake inhibitor. It has been effective in the treatment of depression and is generally well tolerated. There have been problems as noted above with increase blood pressure and there have also been complaints related to sexual function.

Tri-cyclic antidepressants Tri-cyclic antidepressants have long been and in some circles

continue to be the gold standard for the treatment of depression. These medications while they do have quite a few side effects in general have been well tolerated and are effective in relieving symptoms. These medications include imipramine, nortriptyline, amitriptyline, and clomipramine. They all work in varying degrees on the same neurotransmitter systems that have been mentioned above but each to a different degree and with a different level of specificity for a particular neurotransmitter. This difference in neurotransmitter effect and the side effect profiles of each allows a clinician to attempt a good match for treatment with these medications.

Tri-cyclic antidepressants

All of these medications generally have high anticholinergic profiles. Side effects are usually problems with sleepiness, weight gain, dry mouth, constipation, etc.

These medications also generally cause an increase in the time interval associated with the QRS complex as measured with an EKG. This can lead to dangerous arrhythmias during the course of treatment.

Tri-cyclic antidepressants

Because of each of the side effect difficulties listed above these medications can be fatal in overdose. This is generally not seen with the other medications that have been listed above for the treatment of depression. Given that by its very nature depression can have as a core symptom of morbid preoccupation and suicidality these medications must be given cautiously and monitored closely.

Other medications Other medications have been used effectively as adjuncts

to those listed above when treating depression. So called mood stabilizers such as lithium or valproic acid or other anticonvulsants have been used to try and decrease symptoms in a marginally responsive or non-responsive patient. Other medications that have been used with some effectiveness include stimulants and even thyroid hormone supplementation.                                                  

Adolescent girls, who have achieved menarche, and women sometimes respond well to adjuncts of oral or depo contraceptive medications for depressive symptoms.

Electroconvulsive Therapy

While medications have been very effective in relieving the symptoms of depression it should also be noted that electroconvulsive therapy is also a very effective somatic treatment. There are side effects associated with short-term memory problems and the risk associated with anesthesia but overall the patients respond well and quickly to this somatic treatment. Many centers have even moved to offering this treatment in a day hospital setting with no over night stays.  

Bipolar Disorder Bipolar Disorder is seen in children and while it is a

discussion not within the scope of this discussion it can often present in an atypical fashion. Determining core symptoms of grandiosity, racing thoughts or flight of ideas with increased goal oriented pursuits may be difficult to discern and features related to irritability and hypersexuality may be difficult to tease from behaviors of other disorders or problems.

Medications used to treat bipolar disorder are generally called mood stabilizers but there are mood stabilizers in several different classes of medications.

Lithium Lithium has long been the treatment

standard in the psychopharmacologic treatment of bipolar disorder. It is an exceptionally effective mood stabilizer and is generally well tolerated. It does however have several side effects and has a very narrow therapeutic window making it potentially dangerous in overdose. 

Lithium

Side effects include weight gain, diarrhea, acne and less commonly problems with renal function, possible hypothyroidism, and cardiac rhythm problems.

Lithium

Blood levels need to be monitored carefully and care has to be taken in patients that are on medications or participate in activities that would potentially increase the drug’s serum level.

Divalproex (Depakote)

Divalproex (Depakote) is also a very effective mood stabilizing medication. It is generally used as an anticonvulsant but it does currently have approval from the FDA for use as a treatment of acute mania.     

Divalproex (Depakote) Most patients tolerate divalproex (Depakote) with few

problems but there can be side effects. It can lead to some gastrointestinal problems and there can be increased appetite with weight gain. Additionally, in women there has been a correlation between divalproex (Depakote) use and polycysitic ovaries. There have also been problems with liver function, bone marrow changes usually with a decrease in megakaryocytes and subsequently platelets. In very rare cases critical pancreatitis has been a problem. Blood levels need to be monitored while the patient is on divalproex (Depakote) in addition to laboratory investigation of other systems that might be affected.

Other anticonvulsants

Other anticonvulsants used to treat bipolar disorder include but are not necessarily limited to Neurontin, Lamictil, Tegretol, Trileptal, and Topomax. These medications have been generally helpful in treating some of the symptoms of Bipolar Disorder. They have been generally well tolerated, some more than others. They have varying side effects and require different levels of monitoring but all are currently part of the armentareum used for treatment.

“Atypical” Anti-Psychotic Medications

Some of the new so-called “atypical” anti psychotic medications are also being used in the treatment of Bipolar Disorder especially to treat acute manic phase. These include Zyprexa, Geodon, Abilify, Risperdal, and Seroquel. These medications too have been well tolerated by patients but there are some concerning side effects. While they do not have the risk of tardive dyskensia associated with them that the so-called “typical” anti psychotics possess there is still a risk of this potentially irreversible movement disorder. Also each carries risk of acute extra pyramidal side effects including acute dystonias, parkinsonism, and akathesia. All have generally been associated with increased appetite and weight gain and possible increase in baseline glucose levels and lipid levels.

Obsessive compulsive Disorder (OCD)

Obsessive compulsive disorder usually responds well to an appropriate medication regimen. In addition to medication treatment however cognitive and behavioral therapies are important. Also symptoms of preoccupations and perseveration are not necessarily OCD.  

Psychopharmacologic treatment for OCD revolves around the use of medications that affect the serotonergic functions in the brain.

Obsessive compulsive Disorder (OCD)

Any of the selective serotonergic reuptake inhibitors can be very useful in the treatment of OCD. As noted above these medications are well tolerated and possess few side effects. Dosages used to treat OCD are sometimes greater than those used for the treatment of depression and other anxiety disorders.

Selective Serotonergic

Reuptake Inhibitors

These medications include the ones listed above, fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). As noted above, care should be taken in prescribing these medications related to recent concerns about increased suicidal ideations and/or suicidal behavior in children and adolescents taking these medications.  

Clomipramine (Anafranil)

Clomipramine (Anafranil) is a Tricyclic antidepressant medication that has a primary serotonergic action in the brain that has been used for many years in the treatment of Obsessive/Compulsive Disorder symptoms.

Clomipramine (Anafranil)

Side effects with clomipramine (Anafranil) include the usual side effects associated with Tricyclic antidepressants. These are anticholinergic side effects that include increased appetite and weight gain, dry mouth, and constipation. There are also the same concerns associated with a widening in the QRS complex as seen on an EKG. Such a widening in the QRS complex as noted above can lead to problematic arrhythmias. This medication is also extremely toxic in overdose and can lead to death because of the anticholinergic and cardiac side effects associated with it.

Clomipramine (Anafranil)

Routinely, Clomipramine (Anafranil) serum levels should be evaluated periodically. Baseline EKG with routine follow up EKG should be part of the post-prescription care given with this medication

Other medications

Other medications are used to treat symptoms associated with OCD. These medications include other medications that help relieve anxiety. These medications are medications in the Benzodiazepine class and medications, in addition to Clomipramine, that are in the tricyclic antidepressant class. There are at times severe OCD symptoms that seem to be helped by the addition of antipsychotic medications, in particular the newer atypical antipsychotic medications that we have discussed above.

Tourette’s Disorder Tourette’s Disorder is a collection of symptoms

associated with chronic vocal and motor tics. Sometimes these tics can be very complex. In addition to the chronic vocal and motor tics, comorbid issues associated with emotional lability and attention/concentration problems can also be present. OCD is also likely to be comorbid in individuals and in families of individuals with Tourette’s. Both Tourette’s Disorder and OCD can be the result of a post-strep infection autoimmune syndrome.

Tourette’s Disorder

Medications that have been used to treat Tourette’s Disorder include medications that inhibit tic production and also those that decrease anxiety. Of the medications that inhibit tic symptoms whether vocal or motor, the most effective group of medications is the antipsychotic group. These seem to be helpful because they block dopamine activity in the subcortical structures of the brain that are associated with movement. They are generally quite effective in reducing tics, both vocal and motor but do have substantial side effects, as have been noted above.

Risperdal A frequently used antipsychotic medication in the treatment of

Tourette’s is Risperdal. Just as in the treatment of other disorders with antipsychotic medications, care has to be given to monitor for both short-term acute side effects that include extrapyramidal symptoms of parkinsonism, akathisia, and acute dystonias as well as longer-term side effects such as tardive dyskinesia. Additionally, with the chronic use of Risperdal as well as most of the older so-called “typical” antipsychotics, prolactin levels are increased and this can lead to difficulties associated with possible gynecomastia in males, particularly adolescents, and possible lactation and decreased menstruation in females. These atypical antipsychotics, as noted above, are also possibly linked to increased glucose levels in individuals taking the medication and possible increased lipid levels.

Other Atypical Antipsychotics

Other atypical antipsychotics that have been used in the treatment of Tourette’s Disorder include Geodon, Seroquel, and Zyprexa. The newer atypical antipsychotic Abilify, would probably also be useful in decreasing tics in these patients. 

Older So-Called Typical Antipsychotics or Neuroleptics

Older so-called typical antipsychotics such as Pimozide and Haloperidol have also been shown to be very effective in the treatment of Tourette’s Disorder. These medications decrease disruption secondary to tics, both vocal and motor. Both Haloperidol and Pimozide have substantial side effects. These side effects occur at a somewhat higher rate than the typical antipsychotic group. They have been associated with permanent, long-term side effects such as tardive dyskinesia and at a much higher rate than the atypical antipsychotics. Older antipsychotics are also much more likely to have problems associated with acute extrapyramidal side effects. At times, adjunctive anticholinergic medications are needed to decrease some of the worrisome acute side effects of movement associated with the older antipsychotics. Such medicines as Cogentin, Vistoril, Artane, and Benadryl have been used.

Other Medications To Treat Tourette’s Disorder

Other medications have also been used with relative success in decreasing tics in patients with Tourette’s Disorder. They also may have some adjunctive effect in decreasing some of the anxiety associated with Tourette’s Disorder and in helping with some of the comorbid symptomatology associated with decreased attention and concentration. The medications most often used in this particular category are the alpha adrenergic agonists that are centrally acting. These include Quanfacine and Clonidine. Both of these are essentially antihypertensives and acting centrally seem to have some effect on the decrease in tic production. Also by decreasing the overall arousal level, they seem to have a mild anxiolytic effect and seem to increase concentration and attention. Side effects associated with these medications include sleepiness and/or feelings of being tired, both associated with a somnolent effect of the medications and their ability to decrease blood pressure. Care has to be given to monitor blood pressure to ensure that blood pressure does not drop too precipitously. Usually, patients need to be slowly titrated onto these medications and then subsequently slowly titrated off.

Other Medications To Treat Tourette’s Disorder

These include the anxiolytics that have been noted above, including but not limited to, Benzodiazepines, selective serotonin reuptake inhibitors, Tricyclic antidepressants, and other more atypical anxiolytics, including BuSpar.

Psychotic Disorders

Psychotic disorders do occur in children and adolescents but they are not seen as often in this population as in adults.

Anti-psychotic medications

Anti-psychotic medications, both the newer atypical antipsychotic medications and the older typical antipsychotic medications are the mainstays for treatment of psychosis in any individual. The medications that are used in the treatment of psychotic disorders are those that have been mentioned above, including but not limited to, Risperdal, Zyprexa, Geodone, Seroquel, Abilify, and the older more typical antipsychotic medications that include Haldol, Thorazine, Prolixin, Mellaril, Loxitane, and many others. All of these medications, as has been noted above, have substantial side effects associated with them, not the least of which is the possibility of permanent movement difficulty associated with syndromes of tardive dyskinesia.

Benzodiazepines

In addition to these antipsychotic medications in the treatment of psychosis. Benzodiazepines can also sometimes be helpful in treating agitation and irritability that exists alongside the psychotic symptomatology. The use of Benzodiazepines such as Ativan, Klonopin, Valium, etc., can be very helpful in decreasing the morbidity associated with psychotic symptoms.

Conclusion

Psychotropic medications can be helpful adjuncts to mental health treatment in children and adolescents but care needs to be given to ensure appropriate diagnosis and follow up by a professional trained to evaluate and use these medications.

Judicious use in a collaborative atmosphere is essential to success and safety.