Standards for Multiple Psychotropic Drug Use
 Prepared by
Robert S. White, M.D.
(July 1998)


This advisory provides guidelines for interdisciplinary teams in the use of two or more psychotropic medications for people with intellectual disability.


This advisory applies to all individuals of the department for whom the department bears direct or oversight responsibility for their medical care, regardless of the facility or region in which they are served.

The department recognizes the special need to work with facilities which it does not fund or license to ensure the thorough understanding and implementation of medical advisories.


I. Introduction

The use of multiple psychotrophic drugs in psychiatric treatment is increasingly common, both in the general psychiatric population and in dual diagnosis of people with intellectual disability. There are two general types of multiple drug use as follows:

  1. Combination treatment: Using two or more drugs to treat discrete clusters of symptoms and/or diagnoses
  2. Augmentation treatment: Adding one or more drugs to an existing drug, to potentiate and increase the effectiveness of the primary drug.

It should be remembered that psychotrophic drug treatment is rapidly changing, both finding new uses for existing drugs and development of new drugs. These guidelines need to be reviewed and updated at least every two years

II. General principles of multiples psychotrophic drug use:

  1. Any drug used should be indicated for at least one of the person's diagnoses and/or symptom cluster, and should have well defined target symptoms.
  2. In most cases, it is best to start with one drug, selecting the least toxic, and assessing its effectiveness fully before adding other drugs.
  3. Before initiating or changing treatment, define the following:
    1. target symptoms or behavioral equivalents
    2. criteria for success/failure
    3. starting and maximum doses
    4. length of treatment trial
  4. If a treatment failure, consider discontinuing the present drug and switch to a new drug.
  5. If a partial response, consider augmentation by adding one or more augmenting drugs. Augmentation may be with a drug in a different class or a drug within the same class that has a complementary biological action.
  6. If the primary drug successfully treats a symptom cluster but leaves other symptom clusters untreated, consider combination treatment. Combination is usually with a drug in a different class.
  7. Add one medication at a time, define criteria, and wait to get a clear response.
  8. It is almost always best not to be pressured into rushing treatment by not completing adequate trials or adding multiple drugs together because it it then not possible to make any objective judgments about effectiveness.
  9. Always watch diligently for side effects and drug-drug interaction, remembering that self-report isn't reliable.
  10. Re-evaluate the drug combination regularly and try to discontinue and/or reduce doses when possible.
  11. In complex and chronic cases, multiple drug treatment is common and often helpful.
  12. When communication with the person is severely impaired or non-existent, it is much more difficult to make a symptomatic diagnosis. In these cases, treatment is often directed more toward behavior and non-specific diagnoses. Similar principles of treatment apply but treatment should be much more cautious.
  13. There are always exceptions to any guidelines, but any deviation would need to be justified in writing.

III. Specific diagnoses

A. Anxiety disorders

These diagnoses range from acute reactions to chronic and difficult to treat disorders. They are often difficult to diagnose because anxiety is self- reported and often appears, especially in people with moderate to severe intellectual disability, as behavioral equivalents or behavioral regression. Augmentation treatment, especially in chronic cases, is common.

  1. Generalized anxiety: anxiety is secondary to other disorders
    Primary treatment is as follows:
    1. Buspar
    2. Benzodiazepines
    3. Serum Serotonins Reuptake Inhibitors (SSRI) antidepressants
  2. Panic disorder (Agorophobia), Primary treatment:
    1. Benzodiazepines
    2. SSRI antidepressants
    3. Tricyclic antidepressants
  3. Obsessive compulsive disorder, Primary treatment
    1. SSRI antidepressants
    2. Anafranil
  4. Posttraumatic stress disorder (PTSD), Primary treatment
    1. Treated symptomatically
  5. Augmentation treatment
    1. Buspar, a benzodiazepine and/or an antidepressant can becombined safely and is often useful.
    2. More than one antidepressant is usually not effective.
    3. More than one benzodiazepine is usually not effective.

B. Affective disorders

These disorders range from acute reactions to severe and chronic disorders. Diagnosis is usually not difficult in the mild range of intellectual disability, but can be more difficult when the person is non-verbal and there are non- specific behaviors and/or aggression. Careful long-term observation is often productive. Augmentation and combination treatment, especially in chronic cases, is common.

  1. Major depression: (Depressive phase of bipolar disorder and Depression secondary to other mental disorders
    1. Primary Treatment
      1. SSRI anti-depressants
      2. Newer generation anti-depressants
      3. Tricyclic anti-depressants (usually not a first trial because of side effects)
    2. Augmentation Treatment
      1. Second anti-depressant in a different class (i.e., SSRI & tricyclic or SSRI & trazodone)
      2. Lithium
      3. Buspar
      4. Ritalin
      5. Thyroid (T3 or T4)
      6. Atypical neuroleptic
    3. Combination Treatment
      1. Benzodiazepine (for anxiety symptoms)
      2. Traditional or atypical neuroleptic (for psychotic symptoms)
  2. Bipolar Disorder - Manic Phase
    1. Primary treatment of acute phase
      1. Traditional and atypical neuroleptics
      2. Lithium
      3. Depakote
      4. Tegretol
    2. Primary treatment of mood stabilization
      1. Lithium
      2. Depakote
      3. Tegretol
      4. New generation anti-convulsants: (Neurontin; Lamictal)
    3. Augmentation Treatment
      1. A neuroleptic and mood stabilizer often used in acute phase.
      2. Lithium, Depakote and/or Tegretol can be used in combination
    4. Combination Treatment
      1. Neuroleptic (for chronic psychotic symptoms or persistent mania)
      2. Anti-depressant (for depressive symptoms)

C. Psychotic Disorders

These diagnoses are not difficult in people with mild intellectual disability but without reliable verbal self-report, are very difficult to make. Aggression is common. Drug treatment is often not fully effective. Augmentation or combination treatment, while often tried, usually has little effect on the psychotic symptoms.

Schizophrenia, Schizoaffective Disorder, Paranoid Disorder

  1. Primary Treatment
    1. Atypical neuroleptics (preferable for first trial because of side effects and better effect on aggression)
    2. Traditional neuroleptics
    3. Clozaril
  2. Augmentation Treatment
    1. Traditional and atypical neuroleptic
    2. Clozaril and an atypical neuroleptic
  3. Combination Treatment
    1. Benzodiazepine (for anxiety symptoms)
    2. lithium, Depakote, or Tegretol (for mood swings and/or aggression)
    3. Anti-depressant (for depression)

D. Attention deficit hyperactive disorder

Drug treatment is often helpful for people with mild to moderate intellectual disability.

  1. Primary Treatment
    1. Ritalin
    2. dextroamphetamine
    3. Cylert
    4. clonidine
  2. Augmentation treatment is not indicated, but stimulant drugs are often combined with other drugs to treat mixed diagnoses.

E. Autism, Pervasive developmental disorder

Drug treatment is often targeted toward aggression and self-injurious behavior (SIB) symptoms. Treatment success is quite mixed.

  1. Primary Treatment
    1. SSRI anti-depressants
    2. Risperdal
    3. Benzodiazepines
    4. Traditional neuroleptics
    5. lithium and Depakote
  2. Augmentation Treatment: All of these drugs can be combined

F. Non-specific aggression and SIB

It is preferable to make a specific diagnosis when aggression is a symptom but for people with moderate to severe intellectual disability, this is often difficult and non-specific diagnoses such as impulse control disorder are made. Treatment results are mixed.

  1. Primary Treatment
    1. Depakote
    2. Tegretol
    3. lithium
    4. Benzodiaezepines
    5. Beta blockers
    6. SSRI anti-depressants
    7. Buspar
    8. Atypical neuroleptics
    9. Traditional neuroleptics
  2. Augmentation Treatment: All of these drugs can be combined.