The Reality of Adolescent Depression

Transcription

1 Page 1 The Reality of Adolescent Depression Jason Noel, Pharm.D., BCPP Assistant Professor University of Maryland School of Pharmacy Speaker: Jason Noel, PharmD, BCPP is the Director of Clinical Pharmacy Services at Rosewood Center in Owings Mills, Maryland, a 200-bed state-operated residential facility for people with developmental disabilities (DD). Additionally, he is a clinical pharmacy specialist for the inpatient psychiatric services at the University of Maryland Medical Center. He serves as a drug therapy consultant for numerous DD provider agencies throughout Maryland. Dr. Noel s research interests involve the evaluation and improvement of the quality of integrated behavioral and psychiatric treatment for people with developmental disabilities. Speaker Disclosure: Dr. Noel has no actual or potential conflicts of interest in relation to this program This webcast has been supported by an educational grant from Forest Pharmaceuticals This webcast has been supported by an educational grant from Forest Pharmaceuticals PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Accreditation: Pharmacists: L01-P Pharmacy Technicians: L01-T Nurses: N-631 CE Credits: 1.0 contact hour Target Audience: Pharmacists, Technicians & Nurses Program Overview: This program promotes the need for increased awareness of depression in adolescents. About 20 percent of teens will experience teen depression before they reach adulthood. Less than 33 percent of teens with depression get help, yet 80 percent of teens with depression can be successfully treated if they seek help from a doctor or therapist, and many local health clinics offer free or discounted treatment for teens with depression. This program is designed to assist pharmacists in understanding Major Depressive Disorder (MDD), especially in adolescents, as well as the benefits of managing this disorder with medications. The program includes information on pharmacologic treatments, drug interactions, patient counseling, and a question/answer period. Objectives: Review the epidemiology, etiology, and pathophysiology of major depressive disorder in adolescents. Compare and contrast the FDA approved pharmacological approaches to the management of depression to include efficacy, safety, and roles of available treatments. Describe the role of pharmacists can have in identifying, educating and treating adolescent patients suffering from depression This webcast has been supported by an educational grant from Forest Pharmaceuticals Learning Objectives At the conclusion of this knowledge-based activity, the participant will be able to: Review the epidemiology, etiology, and pathophysiology of major depressive disorder in adolescents. Compare and contrast the FDA approved pharmacological approaches to the management of depression to include efficacy, safety, and roles of available treatments. Describe the role health care professionals can have in identifying, educating and treating adolescent patients suffering from depression.

2 Page 2 Epidemiology of Childhood Depression Affects up to 2.5% of children and 8.3% of adolescents in the U.S. Onset of depression appears to be taking place earlier now compared to previous decades Depression in children and adolescents tends to be persistent, recurrent, and more severe into adulthood 5 10% of adolescents with depression will commit suicide within 15 years of their initial episode of major depression Diagnosis Diagnostic criteria for Major Depression is same for children as it is for adults At least five of nine symptoms must be present for a 2-week period How many of the nine symptoms can you list? Please type them in the chat box now! Diagnosis Diagnostic criteria for Major Depression is same for children as it is for adults At least five of nine symptoms must be present for a 2- week period Persistent sad or irritable mood Loss of interest in activities once enjoyed Significant change in appetite or body weight Difficulty sleeping or oversleeping Psychomotor agitation or retardation Loss of energy Feelings of worthlessness or inappropriate guilt Difficulty concentrating Recurrent thoughts of death or suicide Signs in Children and Adolescents Vague physical complaints such as headaches, GI updet, fatigue Problems with attendance and academic performance in school Labile and irritable behavior; outbursts Lack of interest in playing with friends Drug abuse Social isolation, poor communication Fear of death Extreme sensitivity to rejection or failure American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th ed. Text Rev.) 2000.

3 Page 3 Comorbid Conditions Seen in 70% of children and adolescents with major depressive disorder) Dysthymia ( double depression ) Potential development of bipolar disorder Anxiety disorders ADHD Conduct disorders Substance abuse Eating disorders Risk Factors Gender Prevalence is equivalent in childhood Girls are twice as likely as boys to develop depression in adolescence Family History Parents often have history of early-onset depression Others Trauma, abuse Loss of parent/loved one; relationship problems Chronic illnesses Etiology Endogenous Genetic component (esp. in early-onset cases) Decreased activity of biogenic amines Decreases in neurotrophic factor activity Reactive Life stressors General Medical Conditions Endocrine hypothyroidism, Addison s, Cushing s CV HF, stroke, post-mi Neurologic Parkinson s, Alzheimer's, MS Substance-Induced Cocaine withdrawal Methyldopa, beta-blockers, corticosteroids Pathophysiology in Children Lower incidence of hypercortisolemia than in adults cortisol elevations may be seen in young depressed patients close to the period of sleep onset Diminished regional blood flow noted in frontal and temporal brain regions in children with depression Untreated children with depression found to have higher serotonin transporter availability in the hypothalamus and midbrain Children with depression were found to have a reduced frontal lobe volume relative to total cerebral volume

4 Page 4 Depression Treatment Options Psychotherapy Accepted/ Approved Alternatives Pharmacotherapy Psychotherapy Somatic Antidepressants Adjunctive Meds Herbals Nutraceuticals CBT IPT Psychodynamic ECT rtms May provide overall efficacy comparable to antidepressant drugs Drug therapy may show a faster onset and greater efficacy in severe depression Psychotherapy may be associated with lower relapse rates Optimal results seen when combined with pharmacotherapy Provided by trained psychologists, psychiatrists, and social workers American Psychiatric Association. Am J Psychiatry 2000;157(4 Suppl):1-45. Psychotherapy Cognitive-Behavioral Therapy (CBT) Examine and challenge self-defeating thoughts Teaching coping skills and problem solving Effective in children 10 years and older Interpersonal Therapy (IPT) Focus on interpersonal relationships and problems in patients with depression Training on resolving communication problems Electroconvulsive Therapy Application of electrical current to the brain to induce controlled seizures Indicated for severe, refractory depression 80-90% effective Performed as 6-12 treatments 3 times a week May be followed by less frequent maintenance treatments

5 Page 5 Pharmacologic Agents Pharmacologic Agents SSRI s SNRI s MAOI s Fluoxetine* Sertraline Paroxetine Fluvoxamine Citalopram Escitalopram* Amitriptyline Desipramine Doxepin Imipramine Nortriptyline Clomipramine Venlafaxine/desvenlafaxine Duloxetine * FDA-Approved treatments for pediatric patients Phenelzine Tranycypromine Selegiline SRI/S2 Antag NE/DA RI NA/S Antag Nefazodone Trazodone Bupropion Mirtazapine Pharmacology Neurotransmitter Properties Serotonin (5-HT) Improved Mood Modulation of anxiety Sexual dysfunction Nausea/diarrhea Sleep regulation Appetite regulation o Norepinephrine (NE) Improved Mood Fight or flight Cognition Motivation Cardiovascular

6 Page 6 Neurotransmitter Properties Dopamine (DA) Improved mood Psychosis Attention, cognition Reward/reinforcement of pleasurable activities Motor function Neurotransmitter Properties Acetylcholine (ACh) antagonism Urinary retention Dry mouth, constipation Tachycardia Impaired cognition Histamine (H1) antagonism Sedation Weight gain SSRI s MOA Inhibition of presynatptic serotonin reuptake Indications Fluoxetine -- Acute and maintenance treatment of Major Depressive Disorder in patients ages 8 and up Escitalopram -- Acute and maintenance treatment of Major Depressive Disorder in patients ages 12 and up Fluoxetine, fluvoxamine, and sertraline are approved for the treatment of obsessivecompulsive disorder in children and adolescents SSRI Toxicities Activation/jitteriness fluoxetine, sertraline Sedation paroxetine Nausea/diarrhea Decreased platelet aggregation; bleeding risks Hyponatremia Sexual dysfunction (decreased libido, delayed ejaculation)

7 Page 7 SSRI Agent Variables CYP 450 Inhibitors Fluvoxamine 1A2, 2C19, 2D6, 3A4 Fluoxetine 2C19, 2D6 Paroxetine 2D6 Sertraline 2D6, 3A4, 2C9 Drug Active Metabolite t ½ Fluoxetine Norfluoxetine 2-7 days Fluvoxamine None hours Paroxetine None 24 hours Sertraline Desmethylsertraline 26 hours (Es)Citalopram (S-)Desmethylcitalopram days SSRI Withdrawal Syndrome Caused by abrupt discontinuation of shorter half-life serotonergic antidepressants Symptoms Anxiety Irritability, Depressed mood Insomnia Headache Use a gradual taper over a 2-4 week period when discontinuing drug Matching For each drug listed on the left, select the adverse effect/precaution that is most applicable Matching For each drug listed on the left, select the adverse effect/precaution that is most applicable Bupropion Desipramine Venlafaxine Associated with the most significant weight gain Lowers seizure threshold Greatest cardiac risks Bupropion Desipramine Venlafaxine Associated with the most significant weight gain Lowers seizure threshold Greatest cardiac risks Mirtazapine Phenelzine Trazodone Requires adherence to special diet Dose-dependent increases in bp Priapism; significant sedation Mirtazapine Phenelzine Trazodone Requires adherence to special diet Dose-dependent increases in bp Priapism; significant sedation

8 Page 8 Initiating Treatment Symptom Remission Fluoxetine Start at mg daily Patients starting on 10 mg may be titrated to 20 mg after several weeks May consider 5 mg dose (using oral solution or half-tablet) in patients aged 11 and younger Escitalopram Start at 10 mg daily Increase to 20 mg daily after 3 weeks 5 mg dose is available as oral tablet or 5 mg/5 ml solution First Week Decreased Anxiety Improvement in Sleep Improvement in Appetite Increased risk of suicide 1-3 Weeks Increased Activity, Sex Drive, Self-care, and Memory Thinking and Movements Normalize Sleeping and Eating Patterns Normalize 2-4 Weeks Relief of Depressed Mood Less Hopeless/ Helpless Thoughts of Suicide Subside 5 R s of Depression Outcomes Response No symptoms or a significant reduction in depressive symptoms for at least 2 weeks Remission a period of at least 2 weeks and < 2 months with no or few depressive symptoms Recovery absence of significant symptoms of depression (e.g., no more than 1-2 symptoms) for 2 months Relapse a DSM episode of depression during the period of remission Recurrence the emergence of symptoms of depression during the period of recovery (a new episode) Continuation of Treatment Continuation treatment is recommended for at least 6-12 months for all responders to acute treatment Goals are to consolidate response and avoid relapses May consider treatment discontinuation during summer months to minimize disruption to school Maintenance for 12 months or longer may be utilized J Am Acad Child Adolesc Psychiatry 2007;46:

9 Page 9 Antidepressants and Suicide Proposed mechanisms Course of illness Stage shifts spontaneous or drug-induced Side effects activation, insomnia, akathisia, anxiety Direct effect of drug? Suicide Risk Factors Males are at higher risk than females Among males Previous suicide attempts Age 16 or older Comorbid mood disorder or substance abuse Among females Previous suicide attempts Comorbid mood disorder Immediate risk from agitation or major depression Columbia University Study Results from 2006 meta-analysis (n=4582) Encompasses newer antidepressants studied for multiple indications Reports accumulated on suicidal behavior or ideation or possible suicidal behavior or ideation No completed suicides observed in 24 trials Overall relative risk for suicidal behavior for SSRI in depression was 1.66 (CI: ) Fluoxetine: 1.53 ( ) Venlafaxine: 8.84 ( ) FDA Actions : Public health advisories issued due to suicidality reports in children September 2004: Psychopharmacologic Drugs and the Pediatric Advisory Committees review results of Columbia University study Resulted in black box warning for use of antidepressants in children Medication Guides to be provided with every prescription May 2007: Warnings extended to cover young adults aged Arch Gen Psychiatry. 2006;63:

10 Page 10 Treatment-Emergent Suicidality Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated < additional cases Relationship Between SSRI Prescriptions and Observed Suicide Rate (per 100,000) in the US, additional cases fewer case 65 6 fewer cases Food and Drug Administration, Am J Psychiatry 2006;163: Rates of Suicide Attempts During the 3 Months Before and the 6 Months After Initial Antidepressant Prescription Minimizing Risks for Suicidality Evaluate family history Positive/negative responses to antidepressant therapy Screen for bipolar disorder in family members Increase frequency of face-to-face follow-up visits Weekly visits for first 4 weeks Biweekly visits for second 4 weeks Visit at week 12 As clinically indicated beyond 12 weeks If not feasible, provide a means for parents/family/patient to contact HCP if symptoms worsen Medication guides distributed with every prescription Gradual dose titration Avoid highest-risk agents (e.g. venlafaxine) Am J Psychiatry 2006;163:41-47,

11 Page 11 Minimizing Risks for Suicidality Educate parents/guardians to watch for certain behaviors New or more thoughts of suicide or trying to commit suicide New or worse depression, anxiety, or irritability Feeling very agitated or restless Panic attacks Difficulty sleeping (insomnia) Acting aggressive, being angry, or violent Acting on dangerous impulses Being extremely hyperactive in actions and talking (hypomania or mania) Other unusual changes in behavior Case PV, a 16 year old, is brought to the pediatrician with complaints of persistent headache, nausea, low energy and insomnia for three months. Upon further questioning, PV reveals troubling emotional symptoms hopelessness, low selfesteem, and a lack of enjoyment with life. The patient reports occasional alcohol consumption to help minimize these feelings. PV s academic performance has declined. Questions What symptoms of depression are present in this case? What treatment options are indicated? Questions & Answers What education should be provided to PV and parents regarding treatment for depression? Type your questions in the chat box now!