Guidelines in the Treatment of Major Depressive Disorder

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1 Guidelines in the Treatment of Major Depressive Disorder ational Center for Mental Health ueve de Febrero St., Mandaluyong City Telephone o.: Website:

2 ational Center for Mental Health ueve de Febrero St., Mandaluyong City Telephone o.: Website: Organizational Structure OIC, Medical Center Chief II Chief, Medical and Professional Staff (Hospital Service) Chief, Medical and Professional Staff (Community Service) Treatment Protocol Committee Beverly A. Azucena, MD, DPBP, FPPA, MMHoA Beverly A. Azucena, MD, DPBP, FPPA, MMHoA Venus S. Arain, MD, DPBP, FPPA (Life), MHA Bernard B. Argamosa, MD, DSBPP Agnes Joy L. Casiño, MD Joeffrey D. Cruzada, MD, DPBP, FPPA Teresa Rosalie D. Del Valle, MD, DPBP, FPPA, MMHoA Victor C. Vinluan Jr., MD, DPBP, FPPA (Life), MHA l Sign up and open your clinic to the world. 77

3 Algorithm for Major Depressive Disorder 1 Major Depressive Disorder 2 Patient's History (Physical exam, neurological exam, mental status exam, laboratory exam) 3 Does the patient satisfy the DSM 5/ ICD 10 for MDD? 4 Manage patient 5 Is hospitalization indicated? 6 Patient for admission 7 8 Perform alternative diagnosis Out-patient / ER Go to B 9 Management Pharmacotherapy Anti-depressant (Table 2) Antipsychotics (Table 1) Benzodiazepines on-pharmacotherapy Go to A Figure 1 78

4 1 Re-assessment (2-4 weeks) A Mental and physical status Management of adverse/side effects of antipsychotic/antidepressants 2 3 Is patient showing improvement? Continue treatment accordingly 4 Increase dosage of antidepressants 5 6 Is response to treatment adequate after 2 months? Continue treatment accordingly 7 Shift to other class of antidepressants Is response good? Patient continue treatment regime & regular checkup Is response to treatment adequate? Continue treatment accordingly Combination of two antidepressants Patient for admission Go to B Figure 2 l Sign up and open your clinic to the world. 79

5 B 1 4 Patient admitted 3 Is patient manifesting signs & symptoms of psychosis and warrants admission Out-patient 2 MAAGEMET: Pharmacotherapy - see Table 1 & Table 2 With psychosis Rapid neuroleptization olanzapine, risperidone, haloperidol orodispersible tablet or IM inj * closely monitor vital signs Antipsychotics Antidepressants Benzodiazepines Without psychosis Antidepressants Benzodiazepines on-pharmcotherapy 5 Is there a good response? 6 Re-assess 3-14 days Mental & physical status Manage adverse/side effects of medication 7 Refer to mental health facility for possible ECT 8 Does the condition improved during short-term hospitalization? 9 Discharge Continue medication Follow up within 2 weeks 10 Continue treatment in hospital setting until patient improves 80

6 Guidelines in the Treatment of Major Depressive Disorder I. Definition Major Depressive Disorder (MDD) is characterized by a major depressive episode lasting for at least two weeks, without a history of manic, mixed or hypomanic episode. It leads to a significant disruption in one's important areas of functioning such as social/occupational/academic, interpersonal and selfcare. It goes beyond the normal feelings of sadness or grief, with symptoms ranging from appetite and weight changes, sleep disruption, lack of energy, guilt feelings and recurring suicide ideations. MDD carries an extended impact in the society as a whole. The diagnosis of a major depressive disorder requires careful and insightful understanding of the disease process, using mental status evaluations as guided by the American Psychiatric Association's (APA) Diagnostic and Statistical Manual (DSM 5). Although several laboratory examinations are used in patient with depression, these are only done to have a baseline data and that there is no laboratory/ancillary procedure that would definitely point to such a diagnosis. It is important to monitor the treatment course of an individual with MDD, including possible drug interactions and adverse events, because such findings can lead to poor compliance and treatment outcome. II. Epidemiology Among the mood disorders, MDD has the highest lifetime prevalence of almost 17% among psychiatric disorders. Across countries and cultures, there is a twofold greater prevalence of MDD in women than in men which can be explained by a multiplicity of factors such as hormonal differences, effects of childbirth and different psychosocial stressors. The mean age of onset for MDD is about 40 years old, with more than half having an onset between 20 to 50 years old. There is an increased risk of occurrence in individuals without close interpersonal relationships, divorced or separated and can occur with other psychiatric disorders such as substance abuse and anxiety disorders. III. Etiology a. Genetic Factors: umerous studies involving families, adoption and twin studies have long established the genetic basis for mood disorders. The risk of developing a mood disorder ranges from 10-25% for one parent with a disorder, with the risk doubling for both parents afflicted. MDD is the most common form of mood disorder among families with bipolar probands. Major Depressive Disorder b. Biochemical Factors: The involvement of several neurotransmitters, particularly the monoamines (norepinephrine, dopamine, serotonin and histamine), have long been the center of researches regarding major depression. Pharmacologic interventions all aim to target the prominent dysfunctions in these neurotransmitter system. Of the biogenic amines, norepinephrine and serotonin have been implicated the most in the pathophysiology of depression. Other neurotransmitter disturbances include the Acetylcholine, Gamma Amino Butyric Acid (GABA), glutamate and glycine systems which are postulated to have an effect in the evolution of depression. c. europathology: The advent of non-invasive modalities such as Computed axial tomography (CAT) and Magnetic Resonance Imaging have demonstrated an increased frequency of abnormal hyperintensities in sobcortical regions of the the brain. Ventricular enlargement, cortical atrophy and sulcal widening have also been reported. Positron Emission tomography (PET) finding in depression is decreased anterior brain metabolism, more pronounced on the left side. d. Psychosocial and Psychodynamic Factors: It is strongly believed that stressful life events precede first, rather than subsequent, episodes of mood disorders. The most compelling data indicate that the life event most often associated with the development of depression is losing a parent before age 11 and the environmental stressor most often associated with the onset of depression is the loss of a spouse, followed by unemployment and excessive guilt. The psychodynamic theme involving depression is known as the classic view of depression which involves 4 key points: a. disturbances in the infant and mother relationship during the first 18 mos of life predisposes one to vulnerability to depression; b. depression can be linked to a real or imagined object loss; c. introjections as a defense mechanism; d. because the love object is regarded with ambivalence, feelings of anger are directed towards the self. IV. Signs and Symptoms People with depressive illnesses do not all experience the same symptoms. The severity, frequency, and duration of symptoms vary depending on the individual and his or her particular illness. Although depression may occur only one time during your life, usually people have multiple episodes of depression. During these episodes, symptoms occur most of the day, nearly every day. l Sign up and open your clinic to the world. 81

7 DSM 5: An individual diagnosed with major depressive disorder needs to meet all of the following criteria: Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. ote: Do not include symptoms that are clearly attributable to another medical condition. o Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (ote: In children and adolescents, can be irritable mood.) o Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation). o Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly everyday. (ote: In children, consider failure to make expected weight gain.) o Insomnia or hypersomnia nearly every day. o Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down). o Fatigue or loss of energy nearly every day. o Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick). o Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others. o Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. B. The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning. C. The episode is not attributable to the physiological effects of a substance or to another medical condition. D. The occurrence of the major depressive episode is not better explained by schizo-affective, schizophrenia, schizophreniform, delusional disorder or other specified and unspecified schizophrenia spectrum and other psychotic disorders. E. There has never been a manic or a hypomanic episode. Specify if: With anxious distress With mixed features With melancholic features With atypical features With mood-congruent psychotic features With mood-incongruent psychotic features With catatonia With peripartum onset With seasonal pattern V. Management The management of patients with MDD involves a holistic approach which integrates a bio-psychosocial framework. The treatment plan involves two general phases: A. Acute Phase This phase constitutes the first 3 to 6 months of treatment with the general goal of controlling the depressive and psychotic symptoms, if present. Table 1A: Convention/typical antipsychotics Acute dose Maintenance dose Haloperidol Chlorpromazine Table 1B: Atypical antipsychotics Acute dose Maintenance dose Risperidone Olanzapine Clozapine Quetiapine Amisulpride Aripiprazole Table 2: Mood stabilizers Acute dose Maintenance dose Lamotrigine Week 1 & 2: 25 mg PO mg/day in 24 hrly divided doses Week 3 & 4: 50 mg PO 24 hrly Week 5: 100 mg PO 24 hrly or divided doses Lithium carbonate 400 mg - 2 g PO in divided doses for 1 st 5-7 days 1.2 g PO 6-8 hrly Carbamazepine 400 mg/day in divided mg/day PO doses in divided doses Max dose: 1600 mg/day Valproic acid mg/day mg/day (valproate, Max dose: 2.5 g/day Max dose: 3000 sodium valproate) mg/day Valproate 750 mg/day mg/day semisodium Max dose: 60 mg/kg/day (divalproex a) 82

8 This can be done in an out-patient or in-patient setting, if warranted. Hospitalization maybe indicated if the patient is potentially and/or imminently destructive to self and others, lack or absence of satisfactory family support, in severe crises and in patients with diagnostic dilemma. B. Maintenance Phase: This phase involves the next 3-6 months after the acute phase with the prevention of recurrences as the greatest challenge of every clinician. This phase also involves the steady re-integration of the patient to the society and return to premorbid functioning. 1. Pharmacotherapy Selective serotonin reuptake inhibitors (SSRI) Serotonin norephinephrine reuptake inhibitors (SRI) Antipsychotics Benzodiazepines 2. on Pharmacological Behavior therapy Cognitive-behavioral therapy (CBT) Family therapy Group psychotherapy Interpersonal psychotherapy Interpersonal therapy Psychodynamic psychotherapy Supportive psychotherapy 3. Combination of medications and psychotherapy 4. Complementary and alternative therapy l Sign up and open your clinic to the world. 83

9 Index of Drugs Related to the Guideline This index lists the products of interest and/or their therapeutic classifications related to the guideline. This index is not part of the guideline. For the doctor's convenience, brands available in the PPD references are listed under each of the classes. For drug information, refer to the PPD references (PPD, PPD Pocket Version, PPD Tabs, and www. TheFilipinoDoctor.com). ATIPSCHOTICS Atypical Antipsychotics Asenapine Saphris Aripiprazole Abdin Abilify Clozapine Clopax Clopixene Leponex irva Olanzapine Epilanz-10 Olavex 5/Olavex 10 Olazin Olzadin Zyprexa Zyprexa Zydis Paliperidone Invega Invega Sustenna Quetiapine Quekline Queppin Seroquel Seroquel XR Risperidone Renuvie Residon Respixl Riscare Risdin Risperdal Risperdal Consta Risperdal Quicklet Zysda Benzamides Amisulpride Amiabel Solian Butyrophenones Haloperidol Haldol Haldol Decanoas Serenace Zuredel Phenothiazines Fluphenazine Sydepres Chlorpromazine Zycloran Thioxanthenes Flupentixol Fluanxol Fluanxol Depot Other Antipsychotics Lithium carbonate Litcab Quilonium - R ATIDEPRESSATS Selective Serotonin Reuptake Inhibitors (SSRIs) Fluoxetine Adep Drafzin Motivest Prodinl Sertraline Deperin Exulten Zolodin Zoloft Escitalopram Escinal Escivex 5/Escivex 10 Jovia Lexapro Mentumir Zescita Dapoxetine Priligy Paroxetine Seroxat orepinephrine- Reuptake Inhibitors Duloxetine Cymbalta Benzodiazepines Midazolam Midazolex Sedacum Clorazepate Tranxene Anticonvulsants Carbamazepine Carbilepp Tegretol Zynaps Divalproex Depakote ER / Depakote Sprinkle Epival Zystal Lamotrigine Lamictal Motrigine Zyglia Valproic acid Depacon Depakene Syrup Valpros 84

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