Respond about one or more medications in the paper, side effects adverse reactions.

Treatment Options and Adherence Strategies for Patients With Bipolar I Disorder

According to the DSM5 for a diagnosis of bipolar I disorder a person has to meet criteria for a manic episode, which is “a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary)” (2016). There are many treatment options for the acute manic and maintenance phases of bipolar I disorder in the adult population including mood stabilizers such as lithium and valproate, anticonvulsants such as carbamazepine and lamotrigine, and second-generation antipsychotics such as aripiprazole, olanzapine, quetiapine, and ziprasidone (Jauhar & Young, 2019).

In the adolescent population however, there aren’t as many options, as psychotropic medications have differing efficacy and tolerance profiles during this stage of life. Anticonvulsants have not been approved to treat mania in adolescents. Lithium was the first drug approved to treat the acute manic and maintenance phases of bipolar I disorder in adolescents ages 12 and up but because of its narrow therapeutic index indicated by a target trough serum level of between 0.8mEq/L and 1.2mEq/L it is a complicated choice of treatment. To reach this narrow therapeutic window and stay within a safe range, strict medication compliance is necessary, and it has been observed that less than 40% of adolescent patients are adherent to their medication regimen (Munch & Godart, 2016). Additionally, lithium has a wide range of potential side effects including weight gain, nausea, diabetes insipidus, hypothyroidism, tremor, and cardiovascular changes, many drug-drug interactions, and toxicity. Regular blood tests are necessary to monitor lithium levels, thyroid function, and renal function.

Other medications approved to treat mania in adolescents include the second-generation antipsychotics aripiprazole, risperidone, and quetiapine. In fact, the AACAP recommends this class of medication as first line treatment for bipolar disorder in adolescents because of their lower incidents of side effects and toxicity. Initial dosing is usually lower than with adults and titration is slower, however, though adverse effects are less than with other classes of medications, adolescent patients do experience metabolic, motor, and cognitive side effects as well as more sedation, weight gain, and hyperprolactinemia than in adults (Jauhar & Young, 2019).
Troubling side effects are one element contributing to poor adherence to pharmacologic treatment of bipolar disorder. Others include history of nonadherence, longer duration of treatment, increased complexity of treatment regimen, negative beliefs about medications, poor patient-clinician connection, and comorbid substance abuse and personality disorders. Moreover, the short- and long-term consequences of poor adherence include increased rates of relapse, hospitalizations, functional impairment, and suicidality (Guadiona et al., 2008).

Presently, there are a few strategies in practice to increase adherence among patients with bipolar disorder. These strategies include psychoeducation, family involvement, cognitive behavioral therapy, and treatment of comorbid substance abuse. One strategy in particular is especially helpful in increasing behavioral adherence in adolescent patients. The Life Goals Program is a group-based psychosocial intervention which focuses on education and goal setting and achievement. Studies have shown high levels of session attendance, good overall duration of enrollment, high level of session participation, completion of therapeutic assignments, and achievement of functional goals (Guadiona et al., 2008).

Though adherence rates to treatment regimens of bipolar disorder are characteristically low, and even worse among adolescent patients, there are promising techniques to improve compliance. Goal oriented psychosocial interventions have been studied and yield promising results.

References

American Psychiatric Association. (2016). In Desk reference to the diagnostic criteria from DSM-5 (p. 65).

Gaudiano, B. A., Weinstock, L. M., & Miller, I. W. (2008, May). Improving treatment adherence in bipolar disorder: a review of current psychosocial treatment efficacy and recommendations for future treatment development. Behavior modification. https://www.ncbi.nlm.nih.gov/pubmed/18391049.

Jauhar, S., & Young, A. H. (2019, March 27). Controversies in bipolar disorder; role of second-generation antipsychotic for maintenance therapy. International journal of bipolar disorders. https://www.ncbi.nlm.nih.gov/pubmed/30915592.

Munch, G., & Godart, N. (2016). Medscape Drugs & Diseases – Comprehensive peer-reviewed medical condition, surgery, and clinical procedure articles with symptoms, diagnosis, staging, treatment, drugs and medications, prognosis, follow-up, and pictures. https://reference.medscape.com/medline/abstract/27871720.

Review

Encephale

. 2017 Oct;43(5):464-470.
doi: 10.1016/j.encep.2016.09.005.Epub 2016 Nov 18.
[Guidelines for the prescription of mood stabilizers for adolescents: A literature review]
[Article in French]
G Munch 1, N Godart 2
Affiliations expand
PMID: 27871720

DOI: 10.1016/j.encep.2016.09.005

Abstract
Introduction:

Adolescence is a unique phase of the human developmental process. In adolescents, psychotropic medications may have different efficacy and tolerance profiles compared to those at other stages of the lifespan. Mood stabilizers are a complex pharmacological category including lithium, some anticonvulsants, and some second generation antipsychotics. Focusing on this class of pharmacological agents, we aim to answer the following questions: in which indications and according to which modalities should mood stabilizers be prescribed during adolescence?

Methods:

Information was sought from the websites of the French Haute Autorité de santé (HAS) and Agence nationale de sécurité du médicament et des produits de santé (ANSM), the American Food and Drug Administration (FDA) and the British National Institute for Health and Clinical Excellence (NICE). Guidelines from the American Academy of Child and Adolescent Psychiatry (AACAP) were also reviewed. Additional articles were found using PubMed and Google Scholar. We assumed that guidelines published by a national institute were the most relevant, second information from medical academies, then literature reviews, and finally single studies. Practical prescription data were also sought from the French Vidal Drug Dictionary.

Results:

For bipolar disorder in adolescents, lithium has been the first drug licensed in France (from the age of 16) and in the USA (from the age of 12), with indications for acute mania and preventive treatment. Benefits for impulsive and self-aggressive behaviour disorders (especially relevant in case of borderline personality disorder) have also been documented, although lithium has not been licensed in any country for those indications. Extended-release tablets are usually used, at doses targeting for a lithiemia between 0.8 and 1.2mEq/L 12hours after last intake. Because of a narrow therapeutic window and potential side effects (especially nephrotoxicity), lithium prescription requires regular blood tests and good treatment compliance. None of the anticonvulsants has been licensed by a national drug administration as a mood stabilizer in adolescents.

However, the AACAP recommends valproate as a first line treatment for mania, even though the NICE and the ANSM caution that valproate should not be used by women of child bearing age. Besides its teratogenic and endocrine side effects, valproate exposes one to the risk of hepatic toxicity. That is why regular liver function tests should be prescribed when valproate is chosen. According to the AACAP, carbamazepine (which is licensed for the treatment of mania in adults) is not a first line treatment for adolescents. Indeed, no clinical study has demonstrated its efficacy on manic episodes in adolescents. Moreover, carbamazepine exposes one to the risk of agranulocytosis. Lamotrigine has not been approved for adolescents, but some studies suggest its efficacy for bipolar depression (often a treatment-resistant phase) in this age group. Major side effects are the risk of Lyell or Stevens-Johnsons syndrome (which usually occur within the first eight weeks of treatment). There is no need for biological tests, just clinical monitoring. Pharmacological interactions between lamotrigine and oral contraceptives require caution.

Finally, the use of some second generation antipsychotics for bipolar disorder in adolescents has been approved by national drug administrations. In France, only aripiprazole is licensed for acute mania (from the age of 13). In the USA, aripiprazole is licensed from the age of 10 for acute mania and preventive treatment, while risperidone and quetiapine are licensed from the age of 10 for acute mania, and olanzapine is licensed from the age of 13 for acute mania. The AACAP recommends second generation antipsychotics as a first line treatment for bipolar disorder. Moreover, the AACAP and the NICE recommend second generation antipsychotics for behavioural disorders in adolescents. Recommended doses are usually lower and titration slower than for adults. As in adults, adverse effects are metabolic, motor and cognitive disorders. Moreover, hyperprolactinemia, sedation and weight gain are more frequent than in adults.

Discussion:

Epidemiologic data for prescription of mood stabilizers in adolescents only partially concord with recommendations from drug administrations and scientific societies. On the one hand, there is a trend toward preferential prescription of second generation antipsychotics, on the other hand lithium is hardly prescribed to adolescents, less often than anticonvulsants. Thus, without approval from any drug administration, the anticonvulsants are often preferred to lithium (because of lithium’s potential risks due to noncompliance or voluntary poisoning) and to second generation antipsychotics (because of their tolerance profile). Nevertheless, for prescribers it is a complex matter to compare side effects: the frequency and intensity of adverse effects is quite variable from one mood stabilizer to another, and such a thing as an expected value is therefore hard to define. Regardless of the medication chosen, compliance and therapeutic alliance are major issues. Compliance is especially low during adolescence (less than 40% according to a study on bipolar disorder). This lack of compliance has multiple determinants: poor acceptance or misunderstanding of the psychiatric disorder, indirect effects of bad relationships with parents and more generally adults, but also reckless behaviour or death wishes. Improving therapeutic alliance appears as a major challenge for health practitioners dealing with youth. One interesting path of research could be the therapeutic education programs using humanistic communication techniques (addressing both adolescents and their parents) which have already produced encouraging results.

Keywords:

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