Psychopharmacological Treatments in Persons with Developmental Disabilities
Chapter 8 Psychopharmacological Treatments in Persons with Developmental Disabilities (DD)
Chrissoula Stavrakaki, Ruxandra Antochi, Jane Summers, and Judy Adamson Learning Objectives
Readers will be able to: 1. Identify the categories of psychotropic medications 2. Learn how to use psychotropic medications in order to
3. Identify an appropriate monitoring system to deter-
4. Learn the protocols on how to use PRN medications:
• Know at what stage of behaviour it should be
5. Learn what staff need to know about the psychotropic
• Why the medication is being prescribed
• How long before it becomes effective
• Under what conditions the medication should
• How long it is necessary to take the medication
• The adverse effects of the medication
Mental Health Needs of Persons with Developmental Disabilities
Introduction
Try to recollect how frequent the use of medications is in cli-ents with developmental disabilities. Can you understand the multiple uses of these medications? Have you ever wondered what they are for? Professionals and caregivers dealing with persons with developmental disabilities, frequently have tried to use pharmacological treatments (prescribed medications) to treat: •
mental health disorders (i.e., anxiety, depression, schizo-phrenia) and
prevent negative cycles from occurring, such as in Bipolar mental illness.
These medications have also been used to manage : •
maladaptive behaviours whilst definitive and active treat-ment is taking place and
extreme anxiety when rehabilitative intervention is not available or practical.
In many instances, different types of medications are used in an attempt to improve outcome, and to enable the person with a developmental disability and mental disorder to lead a pro-ductive and peaceful life. However, the state of our medical knowledge on medication uses, although better than it has been, is still crude, and in many cases imprecise. During the past ten years, our knowl-edge in assessing, diagnosing and treating persons with mental health problems has improved tenfold. Despite this immense expansion of our database, there are situations where the use of
Psychopharmacological Treatments in Persons with Developmental Disabilities
medication is not the optimal, or the combinations used (polypharmacy) are less effective, or even detrimental. In this chapter, an attempt has been made to: 1. Present the various medication categories mostly used in
2. Discuss possible side effects and how you evaluate them in
3. Create efficient strategies of assessing the needs for medi-
cation use and the different ways of prescribing them (i.e., continuously; on a per needed basis; in crisis/emergency care.
What are psychotropic medications? Psychotropic medications include any prescribed drugs that are given to stabilize or improve mood, mental status or behav- iour. The following categories of medications are commonly used in persons with developmental disabilities:
• Stimulants How to use psychotropic medications in order to minimize their adverse effects
Individuals with DD have risks similar to the general popula- tion with respect to developing the same spectrum of side ef-
Mental Health Needs of Persons with Developmental Disabilities
fects from psychotropic drugs. However, there are a few situa-tions in which these drugs seem to cause adverse effects that are specific to this population, such as epileptic attacks. More-over, individualized response to the medications’ effects is probably higher in people with DD. Thus, their adverse effects may be more unexpected. Presently, for the majority of psy-chotropic drugs, it is difficult to predict, based on scientific evidence, which patients are at risk of experiencing clinically significant side effects. Nevertheless, people with DD may have side effects which may go undetected due to three main factors: • The patient’s functional handicap may mask some signs of
• The individual may experience difficulty in informing
caregivers regarding adverse effects. On one hand, people with a lesser degree of impairment may have the ability to report problems, but they may not be able to understand or appreciate adverse effects as being secondary to medica-tion. On the other hand, patients with more serious diffi-culties may be unable to report adverse effects due to speech or language impairments. For these people, ad-verse reactions may manifest as behavioural changes, such as increased aggression or self-injurious activity.
• Stereotypic behaviours, which are common in people with
DD, may make the recognition of adverse effects very challenging. Differentiating between these behaviours and drug-induced abnormal movements may be difficult. In addition, it is problematic to distinguish between the ad-verse effects of some psychotropic medications, and co-morbid psychiatric or medical conditions (Sovner & Des Noyers Hurley, 1985; Pary, 1993).
Psychopharmacological Treatments in Persons with Developmental Disabilities
It is best to start at low dose when initiating pharmacological treatment, in situations where there is no psychiatric emer-gency and slowly titrate the dose to the lowest optimally effec-tive dose to achieve therapeutic effect. By implementing this approach, the likelihood of experiencing adverse effects may be significantly diminished. Furthermore, it is advisable to avoid frequent medication dose changes in response to the identified target behaviours, which may vary on an ongoing basis. Administration of medication at certain daytime events, such as breakfast or before bedtime, is a good strategy, geared towards promoting compliance with medications used. In ad-dition, use of multiple concomitant medications may signifi-cantly contribute to patient’s problems with compliance and side effects. Thus, it is advisable to minimize them or avoid them if possible (Bergman, 1996; Santosh & Baird, 1999). Rapid discontinuation of most psychotropic drugs may lead to withdrawal reactions. Generally speaking, these medications should be gradually tapered off. In addition, people with DD may be more susceptible to developing withdrawal symptoms secondary to rapid discontinuation of psychotropic medication. However, frequent monitoring during tapering will minimize the occurrence of withdrawal symptoms. Furthermore, pa-tients with DD may present with behavioural changes due to withdrawal symptoms. In some cases, it may be challenging to distinguish between decrease suppression of maladaptive be-haviours or frank symptoms of mental illness or a combination of the two. However, in these cases, giving an immediate dose of the medication being withdrawn may lead to relief of with-drawal symptoms, but with a lack of substantial improvement of the relapse of behavioural problems. In these circumstances, restarting of the last dose of medication, and a more gradual decrease of dosage may facilitate successful discontinuation of
Mental Health Needs of Persons with Developmental Disabilities
the medication (Madrid, State, & King, 2000; Sovner & DesNoyers Hurley 1985). Table 1- Physical checkup prior to the use of
Psychopharmacological agents in Persons with Developmental Disability Category
Complete blood count, blood chemistries with at-tention to liver function tests
Complete blood count, platelet count, blood chemistries with attention to liver function
Note: When pharmacological intervention is established, regu-lar 3-6 months monitoring of the same functions is necessary.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Drug monitoring inactive treatment and or management is nec- essary for medications such as mood stabilizers but not so helpful in antianxiety medications, SSRI’s and antipsychotics excluding Clozapine. How to evaluate for adverse effects
It is important to keep in mind the following strongly advised guidelines: • Baseline physical assessment and laboratory screening
should occur prior to initiation of medication.
• Baseline behavioural assessment is important prior to initi-
ating drug therapy. Target behaviours, signs or symptoms, and quality of life parameters must be defined and quanti-fied. Quantification should be based on empirical measure-ment methods (e.g., frequency count, duration recording, rating scales, time sample, interval recording). Data should be collected over two to four weeks prior to initiating non-emergency medication, and also after the initiation of any psychotropic medication, especially before and after any dose or drug change.
• Anticipate side effects; an increase in behavioural prob-
lems may reflect the adverse effects of a medication.
• Follow-up assessments and laboratory monitoring at regu-
lar intervals (during the initial phase weekly and at least once every three to six months in maintenance).
• Patient, parents and caregivers should be informed about
the potential side effects of the medication and instructed to report immediately any change in behaviour.
• Use open-ended questions when screening for side effects.
Mental Health Needs of Persons with Developmental Disabilities
There are three different types of rating scales used to detect adverse drug reactions: medication-specific, general purpose, and side effect-specific. However, standardized, user-friendly rating scales for monitoring drug-induced side effects are still needed (Reiss & Aman, 1998). Medication-specific scales are based on the most frequently occurring symptoms described in the Physicians’ Desk Refer-ence. They lose their utility when polypharmacy is employed. General-purpose rating scales provide an in-depth review of all body parts, and contrary to medication-specific scales, can be used in patients who take multiple medications. Side effect-specific scales were developed to evaluate the acute and chronic extrapyramidal symptoms secondary to most antipsychotics. Examples include: • Abnormal Involuntary Movement Scale (AIMS) (Guy,
1976) is the most widely recognized and utilized rating scale for routine screening and early detection of tardive dyskinesia. However, this scale is unable to detect tardive dystonias or tardive akathisia.
• Extrapyramidal Symptom Rating Scale (ESRS)
(Chouinard, Ross-Chouinard, Annable, & Jones, 1980) is monitoring for the presence or absence of acute and chronic extrapyramidal side effects (EPSE). On the down-side, this scale does not register the severity of symptoms.
Protocols and Guidelines on how to use PRN Medications
Medications are prescribed to be taken in a certain way (See Table 2). At other times, medications are prescribed to be taken as required (PRN). PRN medications are best used as
Psychopharmacological Treatments in Persons with Developmental Disabilities
follows: Table 2: Abbreviations for Medication and PRN Orders
od
to be given twice a day (usually at 9 a.m. and 6 p.m.)
to be given three times a day (usually at 9 a.m., 1 p.m.
to be given four times a day (usually at 9 a.m., 1 p.m.,
to be given prior to meals (usually 1 hour before meals)
tid a.c. to be given three times a day, prior to meals tid p.c. to be given three times a day, after meals Note: Medications given regularly during the day could be
given at times which are adjusted to accommodate an
PRN medications:
PRN PRN q3h tid can be given every three hours up to three times
Mental Health Needs of Persons with Developmental Disabilities
• Management of extreme anxiety when rehabilitative inter-
vention is not available or practical. For example when a person requires urgent medical attention and is not capable of allowing the medical examination and or treatment to occur. A destinction can be made when a person requires a preplaned intrusive intervention such as a visit to the den-tist. In this case a rehabilitative approach can be more ap-propriate if practical. In situation when this is not avail-able or practical PRN medication can be used.
• Management of an individual’s maladaptive behaviours
while definitive and active treatment of a specific mental disorder is taking place.
The categories of medications used as management strategies in such crises are primarily: • Antianxiety medications/Benzodiazepines. (Please refer to
• Antipsychotic medications. (Please refer to the text)
• Sleep inducing medications. (Please refer to text) Other medication groups have occasionally been used to pre- vent a crisis, but to a much lesser extent, and their usefulness is far more limited. Examples include SSRIs and Beta- Blockers. What we want to achieve when we use medications in crises:
• Primarily and preferably to prevent the crisis from occur-
• To settle already existing escalation of behaviours.
• Minimize damage to self/others and/or property.
Psychopharmacological Treatments in Persons with Developmental Disabilities
• Maintain a less disturbing environment for the wellness
These medications are usually prescribed by psychiatrists, family physicians, dentists, anesthetists, and other relevant dis-ciplines. It has been commonly accepted that environmental, medical and social changes can lead to crises. In any crisis, if time allows, the caregivers have to make an attempt to disen-tangle the reasons and causes for the crisis. In certain situa-tions, however, the escalation of behaviour is so fast and so unpredictable, or it is so extreme in severity, that analysis of causes becomes impossible. In these instances, the clear guidelines and use of PRN protocols are very useful so that any staff/caregiver, familiar or unfamiliar with the person in crisis can respond adequately and appropriately to resolve the problematic situation. An attempt is made to present the reader with certain examples of protocols/guidelines in order to facilitate an appropriate and speedier response in these very traumatic and traumatizing situations.
The Case of John
This case describes individual signs of agitation that can lead to major crisis. John is a 40 year-old male who is diagnosed with devel- opmental disability and Bipolar illness. John lives in a high support group home, and is treated with a mood sta- bilizer in titration.
Mental Health Needs of Persons with Developmental Disabilities
During the titration process John remains excessively overactive and over reactive to environmental stimuli. In this process John’s behaviour can escalate to becom-ing extremely physically and verbally abusive to himself and others. PRN medication is used in order to safe-guard John and others
The protocols/guidelines for John are as follows: Name: John J. Date: 2/4/2002 Psychiatrist/Family Physician: Dr. M. Peterson Medication: Haloperidol 0.5 mg PRN up to 3 mg per 24 hrs Descriptions of Behaviours: Mild Anxiety: Signs of tension occur when John bites his lip, pinches his arm, scratches excessively, or paces and bangs his head. Try to divert John’s attention and lead him to a quiet area. Allow 15 minutes for John to settle. If this fails, then PRN medication is administered. Severe Anxiety/Agitation: Signs of severe anxiety include: yell- ing, threatening staff or clients, obsessing, muttering under his breath. PRN medication is administered immediately. Aggression: Procedure to be followed:
Quiet time, restraint if necessary, PRN as soon as it is
Behaviour/Timeout/Mat restraint Guidelines.
PRN medication should be given when John is able to
Psychopharmacological Treatments in Persons with Developmental Disabilities
Dosages:
• For mild Anxiety: Haloperidol 0.5 mg stat to be repeated
• For Severe Anxiety/Agitation: Haloperidol 1 mg to be
repeated within 30 minutes if necessary.
• For Aggression: Haloperidol 1mg to be repeated if nec-
Note: Any of the above combinations must not exceed 3 mg per 24 hours.
The Case of David
This case presents David, a 47 year old male, who is de- velopmentally disabled and experiences recurrent depres- sive disorder. Four years prior David was treated suc- cessfully and medication was withdrawn. David did well for several years. However, in the past several months he has recurrent symptoms of his depressive condition. Whilst his antidepressant medication is being titrated and to insure David’s safety PRN medication is being used . In addition to his regular medication, David is given oc- casionally PRN medication to prevent behavioral escala- tion.
Mental Health Needs of Persons with Developmental Disabilities
The protocol/PRN guidelines for David are as follows: Name: David L. Date: 6/5/2002 Psychiatrist/Family Physician: Dr. M. Peterson Medication:
Description of Behaviours: David’s signs of severe anxiety are banging head, yelling, pac- ing, whining noises, and frequent visits to the washroom. The following steps should be taken prior to the administration of this medication: 1. Establish verbal communication, and suggest that David
try to relax. Allow him time and a quiet area to do so. Al-low 15-20 minutes time lapse. If David relaxes, please praise him.
2. If above fails, then administer medication. 3. Continue to encourage him to relax. Repeat PRN admini-
stration if the behaviours continue over 30 minutes. Do not exceed recommended maximum.
Note: All PRN administrations must be documented and ac-companied by a behaviour report.
Psychopharmacological Treatments in Persons with Developmental Disabilities
The Case of George
This case presents George, a 35 year old male with Down Syndrome, who experiences generalized anxiety disorder. Despite adequate trial of anti-anxiety medication, George continues to manifest interrupted sleep as well as rapid changes in mood state with periods of both excessive smil- ing and crying. Whilst the team is awaiting to have George reassessed PRN medication is used to prevent self injury or injury of others. .
The protocols/guidelines for George are as follows: Name: George T. Date: 5/4/2002 Psychiatrist/Family Physician: Dr. M. Peterson Medication:
Maximum Dosage:
Description of Behaviours: 1. Inability to relax 2. Intense staring 3. Loud and repeated screaming 4. Physical aggression against another person or property The following steps should be taken prior to the administration of medication:
Mental Health Needs of Persons with Developmental Disabilities
1. Ask George to relax. Allow him time and a quiet area to
2. If this fails, try to redirect him to a quiet area. 3. If he chooses to stay in this area, allow sufficient time to
4. If behaviours continue for more than 20 minutes, or are se-
vere and intense in nature, then administer PRN.
Note: All PRN medication must be accompanied by a behav-iour report. As is evident, PRN protocols/guidelines are very important so that: • medication is used to assist in the management of maladap-
tive behaviours which cannot otherwise be managed safely
• staff/caregivers that are unfamiliar with the person con-
cerned are still able to manage acute behaviour without jeopardizing anyone’s health or safety.
• maximum amounts used per 24 hours are always a must in
order to prevent unwanted side effects or prolonged peri-ods of sedation of the individual client.
It is our hope that the outlined guidelines, as well as the case scenarios, will assist the reader to maximize effectiveness of the PRN medication with minimal risk to health and safety of the individual client and his/her environment.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Description of Psychotropic Medications
A. Antidepressants
Why the medication is being prescribed?
Management of psychiatric states such as: • Major Depression and other depressive disorders
• Body Dysmorphic Disorder and Trichotillomania
High doses of SSRIs are effective in reducing bingeing
Bupropion (Zyban) has been shown to be effective in
smoking cessation when used as a component of an
• These states influence occurrence and severity of behav-
iours, such as aggression, impulsive behaviour, self-injurious behaviour and possibly stereotypy.
How long before antidepressants become effective? Antidepressants are used for treatment of major depression and other depressive disorders. Over 50% of depressed patients will fully recover when an appropriate amount of any antide-pressant is used for at least 6 weeks; whereas, 10-15% will ex-
Mental Health Needs of Persons with Developmental Disabilities
perience some improvement and 20-30% will not improve sig-nificantly. How long is it necessary to take the medication? SSRIs have a better side effect profile than do other antide-pressants. Therefore, they are usually used as the first line of treatment. If there is no improvement after four weeks of the initial dosage, three weeks on a higher dosage should be at-tempted. If no improvement is noted, the diagnosis of depres-sion needs to be re-evaluated. Then, in case the diagnosis is reconfirmed, other antidepressants should be tried, such as Manerix, Trazodone, and Venlafaxine. After a first episode of major depression, treatment is recom-mended for at least 6 months with an antidepressant at the therapeutic dose to which the patient showed response. There-after, the antidepressant should be gradually reduced to dimin-ish the risk of relapse, or the discontinuation syndrome. What are the classes of antidepressants? 1. Selective Serotonin Reuptake Inhibitors (SSRI) As persons with developmental disability have lower seizure threshold, caution should be exercised at the speed of titration of the anti-depressant medication used. Caution should be also exersized when a long acting anti-depressant medication is used such as Fluoxetine in case the diagnosis is incorrect as the adverse effects will be felt for longer periods of time.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Table 3– SSRIs and Recommended Doses Generic Name Brand Name Initial Dose Maintenance Dose Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram
*These are guidelines. Doses may vary on individual basis. What are the SSRIs’ adverse effects?
• Nausea, reduced appetite, vomiting, diarrhea, and gastroin-
testinal discomfort. These side effects may be dose limit-ing, or require therapy changes during treatment with SSRIs. It is possible to minimize these side effects by ad-ministering the medication with or after meals.
• SSRIs (especially Fluoxetine) may lead to agitation and
restlessness at the start of the treatment. SSRIs occasion-ally may cause akathisia (sudden onset of inner restless-ness, irritability, increased energy and insomnia), lasting from a few hours to a day; lowering the initial dose may be beneficial for the patient.
• When agitation associated with SSRIs causes sleep distur-
bance, many clinicians add Trazodone (Desyrel), a sedat-ing anti-depressant, in low doses to alleviate insomnia.
• Other common side effects include excessive sweating,
headache, insomnia, sedation, dizziness, and sexual dys-
Mental Health Needs of Persons with Developmental Disabilities
function (changes in libido, impotence, ejaculatory or or-gasmic disturbances).
• Other adverse effects include rash, dry mouth, urinary re-
tention, weight gain (during long-term treatment).
• Abnormal lab results may occur with SSRIs.
• SSRIs have the benefit of being safe on overdose.
• SSRI withdrawal symptoms include influenza-like symp-
toms, dizziness, nausea, and insomnia; these symptoms may appear even with slow tapering of dosage.
• Serotonin syndrome is usually triggered by the use of mul-
tiple serotonergic drugs, and can be potentially lethal, but resolves with discontinuation of the medications.
• Red flags include: tremor, hypertension, tachycardia, diar-
rhea, myoclonus, ocular oscillations, and in a severe form, may lead to convulsions and even coma.
2. Tricyclic and Tetracyclic Antidepressants Table 4– Tricyclic and Tetracyclic Antidepressants and
Recommended Doses Amitriptyline Clomipramine Anafranil Sinequan Imipramine Tofranil * These are guidelines. Doses may vary on individual basis. **ECG should be done prior to the commencement of TCA’s and during their use. ***Slow titration is advisable unless otherwise indicated as persons with DD cannot communicate the adverse effects of these medications.
Psychopharmacological Treatments in Persons with Developmental Disabilities
What are TCAs adverse effects? • Common side effects: nausea, vomiting, and gastrointesti-
• Anticholinergic effects include dry mouth, blurred vision,
constipation, urinary hesitancy, tachycardia, and may im-pair memory.
• Most patients develop some tolerance to the dry mouth
side effect over time. However, ongoing dry mouth may lead to problems with chewing, swallowing, speaking, in-creased risk of dental carries, denture fit and oral thrush. Treatment includes either stopping these medications, or changing with other medications that have a lower anticho-linergic profile. In addition, other strategies include chew-ing sugarless gum or using sugarless candy, as both stimu-late saliva production. For symptomatic relief, artificial sa-liva (e.g., Moi-Stir, Salivart or Oral Balance) may be bene-ficial for some patients. Finally, to diminish the risk of dental carries, use of sugarless food preparations is recom-mended.
• Constipation is a commonly occurring problem in people
with DD. Constipation and bowel distention are signifi-cant side effects due to potentially severe complications such as obstruction. Therefore, patients taking drugs with anticholinergic properties need adequate monitoring. If constipation develops, dietary fiber, bulk laxatives, stool softeners, and osmotic agents are helpful strategies to use. Fluid intake is also very important in preventing constipa-tion, with eight to ten glasses of water per day being rec-ommended.
• Other adverse effects include sedation, carbohydrate crav-
ing, weight gain, orthostatic hypotension, cardiac effects, tremor, and seizure induction.
Mental Health Needs of Persons with Developmental Disabilities
• TCAs may cause sexual dysfunction including changes in
libido, impotence, or priapism (prolonged, painful erec-tion) especially with Amitriptyline and Desipramine.
• TCA withdrawal may cause nausea, vomiting, diarrhea,
abdominal cramps, chills, cold sweats, headache, and in-somnia within two weeks of abrupt discontinuation.
• Red flags of TCA toxicity include dilated pupils, blurred
vision, dry skin, hyperpyrexia, ileus, urinary retention, confusion, seizures, arrhythmias, and hypotension.
• TCAs overdose can be lethal. 3. Monoamine Oxidase Inhibitors (MAOI) Table 5– MAOIs and Recommended Doses
Brand Name Initial Dose Maintenance Dose
Moclobemide
*These are guidelines. Doses may vary on individual basis. What are MAOIs adverse effects? • Most common are: postural hypotension (which may not
appear until the third to sixth week of treatment), insomnia, agitation, sedation, and sexual dysfunction (impotence).
• Other adverse effects include weight change, dry mouth,
• MAOIs are the most likely to lower seizure threshold and
should be only considered for truly resistant cases.
Psychopharmacological Treatments in Persons with Developmental Disabilities
B. Antianxiety Medications Table 6– Antianxiety Medications and Recommended Alprazolam Clonazepam Rivotril Diazepam Lorazepam Oxazepam Temazepam Restoril
*These are guidelines. Doses may vary on individual basis. 1. Benzodiazepines (BDZ) How long before BDZs become effective? There is a rapid onset of effects within hours. However, the full range clinical response may take several days. Why is it being prescribed? Management of psychiatric states, such as: • Anxiety disorders
Mental Health Needs of Persons with Developmental Disabilities
BDZ alone should only be used for a maximum of
Long-term treatment of insomnia includes behavioural
modification, relaxation techniques, and sleep hygiene.
May consider Trazodone as a non-addictive alternative
How long is it necessary to take this medication? It is recommended to minimize the use of long-acting BDZ be-yond three months. In addition, short-acting BDZ should not be used for more than fourteen days. What are BDZs side effects? • All benzodiazepines can produce sedation and decrease
• The use of benzodiazepines may lead to some impairment
• Cautious use in elderly is advocated given increased sensi-
tivity to sedation, memory impairment, ataxia, risk of falls.
• Hostility, disinhibition, self-injurious behaviour, and ag-
gression are occasionally seen as paradoxical reactions to benzodiazepines, especially in people who exhibit evi-dence of stereotypical, self-injurious behaviours prior to starting treatment with BDZ.
• In case these paradoxical effects occur, close monitoring is
advisable during discontinuation of the BDZ.
• BDZs may cause sexual dysfunction (changes in libido).
• Abuse, tolerance and dependence potential
• Abnormal lab results may occur: thrombocytopenia.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Discontinuation of BDZ should be done on a gradual ba-sis, because rapid taper or abrupt discontinuation may lead to a withdrawal syndrome with symptoms such as rebound anxiety, insomnia, and weakness. In addition, the discontinuation syndrome may present with seizures, confusion, and psychotic symptoms. Furthermore, there is a higher likelihood of occurrence of these symptoms after discontinuation of shorter-acting agents. In these cases, one of the strategies used to decrease withdrawal symptoms is to switch a short-acting agent to a longer acting BDZ prior to starting the tapering. Finally, re-lapse of anxiety disorder need to be considered should symptoms continue for more than two weeks after stop-ping the medication.
Overdose with BDZ alone has a favorable outcome; however, it may be fatal in association with alcohol, an-tidepressants, or antipsychotics. Flumazenil may be used to treat BDZ overdose.
Table 7– Buspirone and Recommended Doses Buspirone
*These are guidelines. Doses may vary on individual basis. **Caution should be excersized when treating symptoms of anxiety when other mental disorders are involved.
Mental Health Needs of Persons with Developmental Disabilities
Why is it being prescribed? Management of psychiatric states, such as:
• anxiety disorders, in particular generalized anxiety disorder
which may influence occurrence and severity of agitation and behavioural problems, including aggression and self-injury.
How long before it becomes effective?
• It takes two to three weeks to achieve its therapeutic ef-
• Headache, nausea, dizziness, and rarely insomnia.
Table 8– Beta-blockers and Recommended Doses Propranolol Pindolol
*These are guidelines. Doses may vary on individual basis. ** Caution Beta-blockers can aggravate depression in persons at risk.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Why is it being prescribed? • Anxiety disorders, in particular social phobia-performance
• Lithium-induced postural tremor (propranolol)
• Neuroleptic-induced acute akathisia (propranolol); which
may influence occurrence and severity of behaviours, such as impulsivity, aggression (propranolol, pindolol)
How long before it becomes effective? • Beta-adrenergic blockers act within one hour of admini-
• For treatment of chronic disorders, the therapeutic effects
may not be seen until four to eight weeks of treatment.
• Treatment should never be discontinued abruptly.
• Beta-blockers need to be discontinued if heart rate is less
than 50, systolic blood pressure is less than 90, or if symp-toms such as dizziness, ataxia, and wheezing occur.
C. Sedatives/Hypnotics
These agents fall into several pharmacological categories: • Antihistamines (e.g., Hydroxyzine, Dyphenhydramine)
• Barbiturates (e.g., Phenobarbital, Amobarbital sodium)
• Chloral derivatives (e.g., Chloral hydrate, Paraldehyde)
• Cyclopyrrolone derivatives (e.g., Zopiclone)
• Imidazopyridine agent (e.g., Zolpidem)
Mental Health Needs of Persons with Developmental Disabilities
Table 9– Mood Stabilizers and Recommended Doses Lithium Carbonate Carbolith, Lithium Carbonate Duralith Long Action
**These are guidelines, doses may vary on individual basis (mg/kg body weight) Why is it being prescribed? Management for psychiatric states such as: • Acute mania and prophylaxis of bipolar illness type I
• Cycloid psychosis (especially in Prader-Willi syndrome
• These states may influence occurrence and severity of be-
How long before it becomes effective?
• Response to lithium alone can take 1 to 3 weeks of treat-
How long is necessary to use mood stabilizers? Mood stabilizer maintenance treatment is indicated in several circumstances:
Psychopharmacological Treatments in Persons with Developmental Disabilities
• after the first episode in patients who are adolescents or 30
• positive family history of bipolar disorder;
• high suicide risk. What are lithium’s adverse effects? • Nausea, vomiting, and gastrointestinal discomfort may oc-
cur. It is possible to significantly reduce these adverse ef-fects by taking the medication with meals, by using sus-tained-release preparations (e.g., Lithobid), or by giving smaller doses more often.
• Diarrhea may occur in patients treated with lithium, par-
ticularly during the first six months of treatment, and when serum lithium levels exceed 0.8. This side effect is impor-tant because dehydration may lead to accumulation of lith-ium with potential intoxication.
• Weight gain may occur. It is difficult to treat, and it may
be partially reversible if lithium is stopped.
• Sexual dysfunction such as priapism may be experienced.
• Intention tremor of upper extremities may be present.
• Lithium-induced hypothyroidism increases with increasing
duration of treatment. People with developmental disabili-ties may not be able to report the symptoms of hypothy-roidism. Therefore, the thyroid functioning should be ade-quately monitored.
• Nephrogenic diabetes insipidus (NDI) are frequently
• People with developmental disabilities should be carefully
monitored for polyuria. Increased urine volume may be
Mental Health Needs of Persons with Developmental Disabilities
problematic to recognize in patients who are incontinent, and wear diapers. In addition, patients with developmental disabilities may have difficulties communicating increased thirst or adequately increasing their liquid intake to coun-teract the effects of polyuria. Moreover, these people may be at higher risk for developing dehydration and severe lithium intoxication. It is essential to address the miscon-ception that polyuria results from excessive fluid intake be-cause restricting liquids may lead to potential intoxication. Therefore, people with lithium related polyuria should be encouraged to have free access to liquids.
• Cardiac dysrhythmias may occur with lithium. Usually
• Dermatological effects can include worsening of eczema,
• Cognitive effects are reported by some patients, including
impaired memory, slowed reaction times, and sedation.
• Abnormal lab results may be observed.
• Lithium toxicity red flags include coarse tremor, speech
difficulty, ataxia, confusion, myoclonus, seizures. Lithium toxicity is a medical emergency; management includes dis-continuation of lithium, and rehydration; hemodialysis is required in most serious cases.
Psychopharmacological Treatments in Persons with Developmental Disabilities
D. Anticonvulsants Table 10– Anticonvulsants and Recommended Doses
Generic Name Brand Name Initial Dose Maint Dose Blood Level
Valproic Acid Depakene Divalproex Na Epival Carbamazepine Tegretol Lamotrigine Lamictal Gabapentin Neurontin Topiramate
**These are guidelines, doses may vary on individual basis (mg/kg body weight) 1. Carbamazepine Why is it being prescribed? Management of psychiatric states such as:
• Acute mania and maintenance treatment of bipolar disor-
• Treatment for these can influence the occurence and sever-
ity of outbursts and aggression; however, carbamazepine has been reported to produce hyperactivity, self-injury, or aggression.
Mental Health Needs of Persons with Developmental Disabilities
How long before it becomes effective? • The anticonvulsant and anti-pain effects have a rapid onset.
However, the antimanic effects take longer to develop.
What are Carbamazepine’s side effects? • Common side effects include: dizziness, ataxia, dysarthria,
• Cognitive effects: may impair memory in some people
• Abnormal lab results may occur. 2. Valproic acid Why is it being prescribed? Management of psychiatric states such as: • Acute mania; many clinicians consider valproic acid to be
a first line antimanic agent for all ages except children un-der 10 due to its potential hepatotoxic side effects in this age group.
• Maintenance treatment of bipolar illness rapid cycling and
mixed states (Valproic acid is the treatment of choice), or
• Treatment of these states may affect occurrence and fre-
quency of associated behavioural outbursts.
Psychopharmacological Treatments in Persons with Developmental Disabilities
How long before it becomes effective? • The antimanic therapeutic effects may appear within one to
What are its adverse effects? • Similar to Carbamazepine 3. Gabapentin Why is it being prescribed? Management of medical/psychiatric states such as: • Seizure disorders
• Anxiety disorders, in particular panic disorder and social
• May be used to alleviate irritability What are its adverse effects? • Common side effects include sedation, ataxia, dizziness,
4. Lamotrigine Why is it being prescribed? Management of biomedical/psychiatric states, such as: • Seizure disorders
• Maintenance treatment of bipolar illness, rapid cycling
Mental Health Needs of Persons with Developmental Disabilities
What are its adverse effects? • Common side effects include headache, dizziness, ataxia,
• Dermatological effects include a rash which may occur in
up to 40% of patients, especially when initial doses are high. Severe rashes, which may lead to Stevens-Johnson syndrome, usually occur during the first eight weeks of treatment.
E. Antipsychotic Agents (Neuroleptics) Table 11– Neuroleptics and Recommended Doses
Brand Name Initial Dose Maintenance Dose
Chlorpromazine Largactil Thioridazine Mellaril trimeprazine Loxapine Perphenazine Trilafon Trifluoperazine Stelazine Fluphenazine Haloperidol Pimozide
**Caution should be exercised in using high doses of neuroleptics because of possible severe side effects especially in persons with Developmental Disability who may not be able to communicate these side effects.
Psychopharmacological Treatments in Persons with Developmental Disabilities
F. Atypical Antipsychotics Table 12– Atypical Antipsychotics and Recommended Clozapine Clozaril Olanzapine Risperidone Risperdal Quetiapine Seroquel Why are they being prescribed? Management of psychiatric states such as: • Psychoses, including schizophrenia, schizoaffective disor-
der, delusional disorder, acute mania, and secondary psy-choses occurring in the context of dementia, brain tumors, Huntington disease, substance abuse.
• Movement disorders such as Huntington disease and
• Management of acute, uncontrollable, severe agitation and
violent behaviour, or stereotypical and self-injurious be-haviour.
How long is it necessary to take this medication? • The duration of therapy with neuroleptics varies with the
nature of the targeted diagnosis, or behaviour for which
Mental Health Needs of Persons with Developmental Disabilities
medication was initiated. In patients who are suffering from schizophrenia, antipsychotics are recommended to be continued for two years for the first episode, five years for the second relapse, and may require indefinite maintenance after the third relapse. When anti-psychotics are used to manage severe maladaptive behaviors, attempts should be made to treat the underlying causes if identifiable and dis-continue them as soon as possible.
What are antipsychotics’ adverse effects? • Convulsant effects may occur.
• Cardiac effects may occur especially with low potency
• Orthostatic hypotension occurs especially with low po-
tency neuroleptics during the first few days of treatment; however, tolerance usually develops rapidly.
• It is important to monitor the blood pressure (lying and
• Sexual side effects such as impotence or ejaculatory and
orgasmic disturbances ay be experienced with antipsychot-ics, expecially Thioridazine. Clozapine and Risperidone may cause priapism.
• Most neuroleptics may lead to weight gain.
• Other side effects may include liver damage, urinary reten-
• Neurological effects may include acute, dose-related neu-
roleptics-induced movement abnormalities, described as extrapyramidal side effects (EPSE). EPSE occur in ap-proximately one third of people with developmental dis-abilities receive neuroleptics. Symptoms usually appear relatively early in the course of therapy with neuroleptics,
Psychopharmacological Treatments in Persons with Developmental Disabilities
especially with more frequent or larger doses, are reversi-ble with discontinuation of medication, and respond to treatment with anticholinergic, anti-Parkinson medications. The EPSE include acute dystonia, neuroleptic- induced Parkinsonism, and acute akathisia (Marsden et al, 1981; Bodfish et al, 1997).
• Tardive dyskinesia (TD) is a movement disorder present-
ing with frequent, repetitive, involuntary movements of the lips, tongue, jaw, face, trunk, or limbs. These abnormal involuntary movements may be exacerbated by emotional stress. In addition, repetitive motor activities or fine motor tasks may worsen TD. On the other hand, trying to volun-tarily control these symptoms may either relieve or accen-tuate the abnormal movements. However, TD symptoms may diminish with relaxation, and are absent during sleep. The prevalence of TD in the population with DD is quite high. Up to one third of children and adults receiving neu-roleptic medication have been reported to develop TD. Risk factors for TD include length and degree of neurolep-tic exposure, dosage and age. However, TD may appear in persons without histories of neuroleptic exposure.
• Neuroleptic malignant syndrome (NMS) is a rare, but po-
tentially fatal adverse effect of all antipsychotics. NMS symptoms include muscle rigidity (lead pipe rigidity) or catatonia, instability of the autonomic nervous system (hypertension or labile blood pressure, arrhythmias, dilated pupils, sweating, and incontinence), rapid onset of fever, and altered mental status (confusion, agitation, stupor). (Boyd, 1993).
Treatment involves stopping the causative medication,
adequate hydration, and possibly using a dopamine
agonist (Bromocriptine), or a muscle relaxant
Mental Health Needs of Persons with Developmental Disabilities
Signs and symptoms of overdose include dilated pu-
pils, EPSE, increased heart rate, and low blood pres-
sure. The overdose usually has a favorable prognosis
except for Thioridazine and Mesoridazine due to their
cardiotoxic side effects. In addition, the outcome of
neuroleptic medication overdose is more guarded in the
presence of alcohol and benzodiazepines; complica-
tions include delirium, respiratory depression, and sei-
Nausea, vomiting, decreased appetite, behavioural
changes, decreased sleep, sweating, abnormal move
ments, and seizures have been reported. These
symptoms usually occur after long-term treatment, and
A gradual reduction of 10% to 25% of the original dose
every two to four weeks may be helpful in avoiding or
minimizing these withdrawal symptoms. Low-dose
Lorazepam or Propranolol may be helpful in managing
• Atypical antipsychotics have less side effects than do typi-
G. Stimulants Table 13– Stimulants and Recommended Doses
Brand Name Initial Dose Maintenance Dose
Methylphenidate Methylphenidate Ritalin SR Dextro-amphetamine Dexedrine Dextro-amphetamine Dexedrine Spansules
Psychopharmacological Treatments in Persons with Developmental Disabilities
Why are they being prescribed? • Attention deficit hyperactivity disorder (ADHD) What are their adverse effects?
• Stimulants may exacerbate tics, obsessions, compulsions,
epilepsy, anxiety, or psychotic features.
• Growth delay, anorexia and weight loss in children
• Difficulty falling asleep, nightmares
• Hair loss and hematological side effects are rare.
• Stimulants withdrawal may lead to symptoms of dyspho-
ria, depression, fatigue, hypersomnia, and hyperphagia.
Summary
This chapter provides the reader with a list of prescribed medi- cations (pharmacotherapy) used in persons with dual diagno- sis - (developmental disability and mental disorders). An at- tempt has been made to encourage clinicians, caregivers, and families to use psychotropic medications only when a psychi- atric diagnosis is supported. It is understood that from time to time these medications may be used to manage acute and vio- lent behaviours. In these instances, however, every effort has to be made to initiate other rehabilitative interventions when- ever possible. The various categories of these pharmacological treatments are outlined in groups that are addressing different mental health/behaviour problems. This chapter also offers a list of desirable/ undesirable (side-effects) effects of all medi- cations listed. An attempt has been made to provide the sever- ity and malignancy of the side effects in an effort to assist the
Mental Health Needs of Persons with Developmental Disabilities
reader in his/her clinical decisions as to the subsequent steps necessary to be followed in the resolution of the medical/mental crises resulting from the medication used. Guidelines for use of medications in various ways (i.e., continuous, on an as per needed basis, in crisis) are also provided. The most important steps to be followed in a situation where a client is thought to be suffering from mental disorder/s is the following Axis: 1. Think of mental disorder as a possible explanation of cer-
2. Assess the problem behaviour. 3. Diagnose the problem as a mental disorder. 4. Treat the problem with medication whenever appropriate. 5. Follow-up to determine:
- maintain a minimal level of medication necessary to
- physical checkup re other physiological functions that
can become affected by the prolonged use of
It is to be remembered that the client is in the centre of our car-ing, and that various pieces of the puzzle of wellness/disease are necessary to be in place in order to maximize the beneficial effects of all of the parts, and enhance the quality of life of persons with a dual diagnosis.
Psychopharmacological Treatments in Persons with Developmental Disabilities
Do You Know?
1. What are the categories of psychotropic medica-
2. For each category of medication, describe indica-
tions, mechanism of action, duration of treatment, side effects, and conditions under which the drug should be discontinued.
3. How would you use psychotropic drugs in order to
4. How would you monitor for side effects? 5. What are the protocols on how to use PRN medica-
Resources Bezchlibnyk-Butler, K.Z. & Jeffries, J.J. (Eds.) (1998). Clini- cal handbook of psychotropic drugs, Eighth Revised Edi-tion. Seattle, WA: Hogrefe & Huber Publishers.
Kaplan, H.I. & Sadock, B.J. (1997). Synopsis of Psychiatry,
8th edition, Baltimore, MA: Williams & Wilkins Company
Kutcher, S.P. (1997). Child and adolescent psychopharmacol-ogy. Philadelphia: W.B. Saunders Company
References
Bergman, J.D. (1995). Psychopharmacologic treatment of neu-
ropsychiatric conditions in mental retardation. Pediatric Psychopharmacology: Child and Adolescent Psychiatric Clinics of North America, 4(2), 401-433.
Bergman, J.D. (1996). Pharmacologic interventions: Mental
retardation. Child and Adolescent Psychiatric Clinics of
Mental Health Needs of Persons with Developmental Disabilities
Bezchlibnyk-Butler, K.Z. & Jeffries, J.J. (Eds) (1998). Clini-cal handbook of psychotropic drugs (8th Revised Ed.) Se-attle, WA: Hogrefe & Huber Publishers.
Bodfish, J.W., Newell, K.M., Sprague, R.L., Harper, V.N., &
Lewis, M.H. (1997). Akathisia in adults with mental retar-dation: Development of the akathisia ratings of movement scale (ARMS). American Journal on Mental Retardation, 101(4), 413-423.
Boyd, R.D. (1993). Neuroleptic malignant syndrome and
mental retardation: Review and analysis of 29 cases. American Journal on Mental Retardation, 98(1), 143-155.
Chouinard, G., Ross-Chouinard, A., Annable, L., & Jones, B.
D. (1980). Extrapyriamidal symptom rating scale. Cana-dian Journal of Neuroscience, 8, 164-166.
Dorland’s Medical Dictionary (24th Ed.) Philadelphia: W.B.
Guy, W. (1976). Abnormal involuntary movement scale. In
ECDEU assessment manual for psychopharmacology (Revised). PHEW publication ADM 76-338 (pp. 534-537). Washington, DC: US Government Printing Office.
Kaplan, H.I. & Sadock, B.J. (1998). Synopsis of psychiatry
(8th Ed.) Williams & Wilkins Company
Kutcher, S.P. (1997). Child and adolescent psychopharmacol-ogy. Philadelphia: W.B. Saunders Company
Kutcher, S. (2000). Practical clinical issues regarding child
and adolescent psychopharmacology. Child and Adoles-cent Psychiatric Clinics of North America, 9(1), 245-260.
Madrid, A.L., State, M.W., & King, B.H. (2000). Pharma-
cologic management of psychiatric and behavioral symp-toms in mental retardation. Psychopharmacology: Child and Adolescent Psychiatric Clinics of North America, 9 (1), 225-243
Psychopharmacological Treatments in Persons with Developmental Disabilities
Marsden, C.D. & Schachter, M. (1981). Assessment of ex-
trapyramidal disorders. British Journal of Clinical Phar-macology, 11 (2), 129-151
Medical Economic Date. (1966). Physician’s desk reference.
Pary, R. (1993). Psychoactive drugs used with adults and eld-
erly adults who have mental retardation. American Journal on Mental Retardation, 98(1), 121-127
Reiss, S. & Aman, M.G. (1998). Psychotropic Medications
and Developmental Disabilities. In S. Reiss & M.G. Aman (Eds.), Psychotropic medications and developmental dis-abilities: The International Consensus Handbook (pp. 45-72). Ohio State University: Nisonge Centre.
Santosh, P.J. & Baird, G. (1999). Psychopharmacotherapy in
children and adults with intellectual disability. LANCET, 354, 233-242
Sovner, R. & DesNoyers Hurley, A. (1985). Assessing the
quality of psychotropic drug regimens prescribed for men-tally retarded persons. Psychiatric Aspects of Mental Re-tardation Reviews, 8/9, 31-38.
Silka, V.R. & DesNoyers Hurley, A. (1999). When do you
decide to use an antipsychotic medication? Mental Health Aspects of Developmental Disabilities, 2(1), 33-35
Acknowledgements
Special thanks to Steven Weisblatt for his invaluable contribu- tion to this chapter.
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