Vinks and Walsons (2003) indications for therapeutic drug monitoring are listed in TABLE Factors to Attend to in Medication Monitoring.
TABLE Factors to Attend to in Medication Monitoring
|Higher than standard dose required|
|Serious and persistent side effects|
|Suspected drug-drug interactions|
|New preparations, changing brands|
|Presence of other illnesses such as hepatic, renal, inflammatory diseases, and others|
Annotations to the tim a algorithm (2003) from a child and adolescent psychiatric perspective
Choice of antipsychotic (AP) should be guided by considering the clinical characteristics of the patient and the efficacy and side effect profiles of the madication.
Any stage(s) can be skipped depending on the clinical picture or history of antipsychotic failures.
First episode or never before treated with a NGA
Notes to the Algorithm
1. Since the research data-based for constructing algorithms on children and adolescents is limited, by necessity the algorithms for the use of atypical antipsychotics for children and adolescents are preliminary or tentative and largely borrowed from the ones constructed for adults. The algorithm under discussion is based on the TIMA Antipsychotic Algorithm (2003).
2. Every new onset psychotic episode in children and adolescents necessitates a comprehensive psychiatric evaluation complemented with pertinent medical, neurological, laboratory and imaging studies. See “Aids in the Diagnosis of Psychosis,” chapter 5, and chapters 6 and 7 for the differential diagnosis of psychotic disorders in children and adolescents. Parallel considerations will be applied to situations of relapse or deterioration of clinical condition. Attributing deterioration to the illness clinical course may be erroneous.
3. There are no pediatric algorithms for the treatment of schizophrenic disorders in childhood. Child and adolescent psychiatrists, and adult psychiatrists who treat child and adolescent psychosis seek guidance from the adult algorithm. The CATIE results are likely to promote a change in the schizophrenia algorithm. This writer believes that a reconsideration of some first generation antipsychotics will be in order, based on perphenazine therapeutic effectiveness, tolerability and cost-effectiveness when compared with second generation antipsychotic comparators (olanzapine, risperidone, ziprasidone, and quetiapine). In this writer’s opinion the “big winner” in the CATIE trial was perphenazine: it performed as well as the other atypicals at a low dose (about 200 mg of chlorpromazine equivalence/day), had good tolerability, and cost far less than the competitor atypicals. The initial CATIE results raise serious questions about the present schizophrenia algorithm. It appears that the second generation antipsychotics’ effectiveness and tolerability is not equal; it seems that there are gradients of therapeutic superiority of some atypicals over others, and that some atypicals have serious issues with tolerability. Changes in the current algorithm are likely in the near future.
4. This writer recommends the use of antipsychotic medications that have significant data-base, level 1 evidence (as first-line medication for treatment of psychotic disorders in children and adolescents.
5. This writer objects to the present TIMA antipsychotic algorithm as a clinical guide for the psychopharmacological treatment of severe psychosis of childhood:
(a) There is no evidence base to support the use of aripiprazole, olanzapine, ziprasidone, or quetiapine as first-line medication in childhood for the treatment of primary psychosis in childhood. There is supportive controlled data for the use of risperidone as a first-line agent for psychotic disorders in children and adolescents.
(b) The CATIE study would suggest that perphenazine should be considered, at least at the same level, than risperidone, ziprasidone, or quetiapine.
(c) If other studies confirm the therapeutic superiority of olanzapine, this medication will need to be considered as a first-line medication against severe psychosis of childhood. The CATIE II results, adds support for this consideration. Since this medication is associated with frequent metabolic toxicity the initiation of this medication will necessitate the compulsory implementation of protective measures to decrease the metabolic risks; these include: dietary counseling, promotion of regular exercising and fitness, and the concomitant use of weight attenuating medications.
(e) This writer considers the use of perphenazine and mood stabilizer early in the nonresponsive downward track rather than using these drugs as the last resort choices prior to consideration of clozapine or ECT.
(f) It is unclear what will be the role of emerging electrical and magnetic brain stimulating technologies and how proven psychosocial paradigms will need to be implemented to enhance the pharmacological interventions.
(g) Psychopharmacologic treatment needs to be complemented by ongoing psychosocial interventions. Appropriate psychoeducational programming is fundamental. Other interventions (i.e., speech and language therapy occupational therapy physical therapy) will be implemented as pertinent; medical and other ancillary services will be accessed as necessary.
6. Since the long-term consequences of extended use of atypical medications in children and adolescents is unknown, systematic medication side effect risk monitoring, including pertinent laboratory monitoring, is mandatory. The psychiatrist will be attentive to learning interferences created by medication side effects or the presence of comorbid disorders. Attention to the learning processes and to concentration difficulties, in particular, are central concerns for pediatric patients. Stimulant medication or alternative treatments to deal with comorbid ADHD may be necessary.
7. Because chronic psychotic youth have a higher risk for suicide or even homicidal behaviors, these risks will need to be monitored on a regular basis. Psychiatrists will be equally attentive to the use or abuse of alcohol or other illegal drugs, common complications of chronically psychotic patients.
8. The psychiatrist will also be attentive to the issues of medication compliance and to adherence to other psychosocial treatments. Early changes to alternative medications are in order if tolerability is compromised or there is a lack of therapeutic effectiveness. Sensitive use of antidepressant, antianxiety medications or others are indicated when there is significant depressive, anxiety or additional comorbidity A mood stabilizer maybe indicated if there is indication of mood instability or if the psychiatrist is seeking augmentation effects.
9. Psychosocial interventions, including appropriate psychoeducational programming, and ongoing individual and family interventions, are essential components of the comprehensive treatment plan for chronically psychotic children. The psychiatrist will monitor compliance to these interventions in each follow-up appointment.
Li = Lithium
DVP = Divalproex
AAP = Atypical Antipsychotics
Olanzapine, Quetiapine, Risperidone, Clozapine, Aripiprazol, ziprasidone. AC = Anticonvulsants
Following the recommendations for monitoring weight, diabetes, and dyslipidemias related to second generation antipsychotics, the Consensus Development Conference guidelines could be modified for children and adolescents in the following manner: A modification of the Consensus Development Conference is presented in TABLE Monitoring Recommendations for Weight, Diabetes, and Dyslipidemias.
For patients with a higher risk for diabetes and those treated with other medications that may increase this risk (e.g., valproate, lithium, depoprovera), it may be preferable to initiate treatment with an second generation antipsychotic that appears to have a lower propensity to induce weight gain or glucose dysregulation.
TABLE Monitoring Recommendations for Weight, Diabetes, and Dyslipidemias
|Baseline||1st month||2nd month||3rd month||6th month||1 year|
|Personal and family history||X||X|
1. or more often if an illness emerges
2. or more frequently if there is a rapid increase of weight or BMI
3. or more frequently if there is a rapid increase of weight or BMI
4. or more frequently it there is emergence of dizziness or related symptoms
5. or more often if diabetes related symptoms (polydypsia, polyphagia, polyuria, or others) unfold.
6. or more frequently if there is a rapid increase of weight or BMI
7. or more often if the person has Acanthosis Nigricans, history of diabetes, or if the patient has gained weight or BMI rapidly
8. or more often if the patient has a cardiovascular history or if dizziness, fainting, chest pain, or related symptoms develop