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Slide 2 Disclosures Speakers Bureau: Otsuka and Lundbeck Off-Label Uses Will Be Discussed Slide 3 Objectives Review Common Psychiatric Diagnoses presenting in the primary care setting Review available pharmacologic treatment options Slide 4 Depressive Disorders History Prevalence: 15% total, 25% woman Cost: estimate $45-55 Billion annually in U.S. Treatment: 2/3 of people with depression do not realize they have it (Andrew, 3/2012) and only 20% of those diagnosed received appropriate treatment Slide 5 Depressive Disorders Depressed patients lose on average 5-6 hours of productive work every week Depressed patients are more than 2 times likely to take sick days Depressed patients are 7 times more likely to be unemployed Slide 6 Depressive Disorders Depressed patients have an 11% decrease in the probability of getting married Patients have a 35% decrease in lifetime income due to depression Rates of undetected depression among drug and alcohol users are estimated to be at least 30% Slide 7 Depressive Disorders According to WHO, depression was the 3 rd most important cause of disease burden worldwide in 2004 A Toronto study showed workers who were treated for severe depression were 7 times more likely to be high performing than those who were not Slide 8 Epidemiology Sex Women > Men Age Mean age of onset 40 years old Race Not differ from race to race Socioeconomic No correlation Marital Status Higher if no close relationships, divorced, separated Slide 9 Etiology Cause Unknown Causative factors divided into biological factors, genetic factors, and psychosocial factors Biological Factors Mood disorders associated with dysregulations of biogenic amines norepinephrine, serotonin, dopamine Adrenal Axis: Hypersecretion of cortisol Thyroid Axis: Abnormal regulation, autoimmune disorder (10% have antithyroid antibodies) Growth hormone: Blunted sleep induced stimulation of growth hormone release Slide 10 Etiology Genetic Factors: Data strongly suggestive of genetic component Pattern unknown Family studies 1 st degree relatives 2 to 10 times more likely Adoption studies Biological children reared in non affected adoptive family Twin studies 50% in monozygotic twins Slide 11 Diagnosis DSM IV-R specific diagnostic criteria Qualifiers: Severity, Psychotic, Recurrent, Single, Remission Significant distress, functional impairment Not due to direct physiological effects of a substance Not better accounted for by bereavement Symptoms not persist > 2 months after loss Not suicidal, no significant functional impairment Slide 12 Clinical Features Depressed Mood: Subjective or observation Marked decrease interest Decrease/Increase appetite, weight change Sleep disturbance Psychomotor agitation/retardation Loss of energy Guilt, worthlessness Poor concentration, indecisiveness Recurrent thoughts of death, suicidal thoughts Slide 13 Differential Diagnosis Bipolar Disorder Dysthmia Cyclothymia Schizoaffective Disorder Schizophrenia Anxiety Disorders Personality Disorders Substance related Disorders Uncomplicated Bereavement Premenstrual dysphoric Disorder PostPartum Depression Depression 2 nd to General Medical Condition Infections Endocrine Disorders Neurological Disorders Neoplasms Inflammatory Disorders Slide 14 Course and Prognosis Course Chronic and Relapsing course Untreated: 6-13 months Treated: 8 weeks 3 months 20 year period: mean number 5-6 episodes If hospitalized, 75% recur within 5 years Prognosis Poor if: coexisting dysthymic disorder, alcohol abuse, anxiety disorders, multiple episodes, hospitalization, men, poor support, personality disorder, late age initial onset, psychotic component Slide 15 Treatment 1st Safety 2 nd Safety 3 rd Safety First Decision to make Do you hospitalize the patient? Voluntary vs. Involuntary Slide 16 Suicide 15% of depressed people take their own lives Risk Factors Male Elderly Caucasian History of previous suicide attepts Co-Morbid medical illness Drug/Alcohol use Co-Morbid psychiatric illness Social isolation, poor social support Low job satisfaction, financial stress Slide 17 Pharmacologic Options Tricyclics SSRIs SNRIs MAOIs Other classes Slide 18 Tricyclic Antidepressants Common Uses: Depression* Neuropathic and Chronic Pain Headache Insomnia Anxiety OCD* (Clomipramine Anafranil) Enuresis Slide 19 Common Tricyclics Amitriptyline (Elavil) Nortriptyline (Pamelor) Imipramine (Tofranil) Despiramine (Norpramin) Clomipramine (Anafranil) Doxepin (Sinequan) Trimipramine (Surmontil) Protriptyline (Triptil) Slide 20 Tricyclic Antidepressants Mechanism of Action Block reuptake of norepinephrine Common Side Effects Anticholinergic Dry mouth, constipation, urinary hesitancy Cardiovascular Hypotension, palpitations, conduction slowing CNS Tremor, sedation, stimulation Other Weight gain, sexual, perspiration Common Drug Drug Interactions CNS depressants: Sedation SSRIs: Increase TCA levels MAOIs: Serotonin Syndrome Tramadol: Increase Seizure Risk Antihypertensive drugs: May alter affect Slide 21 SSRIs Common Uses: Depression Panic Disorder Generalized Anxiety PTSD OCD Social Anxiety PMDD Slide 22 Common SSRIs Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro) Fluvoxamine (Luvox) Slide 23 SSRIs Mechanism of Action Block Selectively Serotonin Reuptake Common Side Effects GI, CNS activation, sedation, sexual, weight gain, HAs Common Drug Drug Interaction TCAs MAOIs: Serotonin Syndrome Warfarin, NSAIDs: potential increase risk of bleeding Tramadol: Increase seizure risk Slide 24 SNRIs Common Uses: Depression* Generalized Anxiety* Social Anxiety* Panic Disorder* PTSD PMDD Chronic Pain* Fibromyalgia* Slide 25 Common SNRIs Venlafaxine (Effexor) Duloxetine (Cymbalta) Desvenlafaxine (Pristiq) Slide 26 SNRIs Mechanism of Action Blocks Serotonin and Norepinephrine Reuptake Common Side Effects Similar to SSRIs HTN Drug Drug Interactions MAOIs: Serotonin Syndrome Tramadol: Increase seizure risk Warfarin, NSAIDs: Potential increase risk of bleeding Slide 27 MAOIs Common Uses: Depression* Social Anxiety Panic Disorder Parkinsons* (Selegiline) Dementia Slide 28 Common MAOIs Selegiline (EMSAM) Phenelzine (Nardil) Tranylcypromine (Parnate) Isocarboxazid (Marplan) Slide 29 MAOIs Mechanism of Action Blocks MAO from breaking down norepinephrine, serotonin, dopamine Common Side Effects Orthostatic hypotension, hypertensive crisis, sexual, sedation, insomnia Drug Drug Interaction High Tyramine Foods SSRIs SNRIs TCA Meperidine Dextromethorphan Carbamazepine Bupropion Beta-Blockers Sympathomimetics Slide 30 Otherclasses and Newer Agents Bupropion Mechanism of Action: NDRI Common Side Effects: headache, insomnia, tremor, anorexia, seizures (rare) Drug Drug Interaction: TCA (increase), MAOIs, Tramadol Slide 31 Other Classes and Newer Agents Mirtazapine (Remeron) Mechanism of Action: alpha 2 antagonist, dual serotonin and norepinephrine agent Common Side Effects: appetite increase, sedation, weight gain, dry mouth, hypotension Drug Drug Interaction: MAOIs, Tramadol Slide 32 Other Classes and Newer Agents Vilazodone (Viibryd) Mechanism of Action: Serotonin partial agonist reuptake inhibitor Common Side Effects: Nausea, diarrhea, vomiting, sexual (? Less), brusing Drug Drug Interactions: MAOIs, Tramadol, SSRIs (increase levels), Carbamazapine (decrease levels) Slide 33 Other Classes and Newer Agents Levomilnacipran (Fetzima) Milnacipran (Savella) FDA approved only for fibromyalgia Levomilnacipran is a left isomer of milnacipran Not approved for treatment of fibromyalgia Indication: Major Depression Mechanism of Action: SNRI Common Side Effects GI, sexual, sweating, palpitations, hypertension, bruising Slide 34 Other Classes and Newer Agents Vortioxetine (Brintellix) Mechanism of Action: SRI (?) Indication: Major Depression Common Side Effects: GI, dizziness, sexual, bruising, Drug Drug Interactions: MAOIs, SSRIs, SNRIs, Warfarin, NSAIDs Slide 35 Treatment Strategies Depression Where to begin? If it works, what next? Length Monitoring If it doesnt work, what next? Dosing Augment Switch Diagnosis Therapy Slide 36 Partial Responders/Augmentation Dose? Diagnosis? Medical? Substance use? Combination of Antidepressants Lithium Thyroid Stimulants Atypical Antipsychotics Buspirone Slide 37 Treatment Options Beyond Pharmacotherapy Psychotherapy ECT PhotoTherapy Magnetic Stimulation Slide 38 The Good News Treatment Responsive Satisfying to Treat Major Impact on Quality of Patients lives, family and society Improved Response to Medical Treatment and Prognosis Cost Effective Treatment Slide 39 Anxiety Disorders Anxiety disorders are the most common class of mental disorders present in the general population Affecting 40 million adults in the US in a given year Only 1/3 suffering receive treatment Cost $42 billion a year direct/indirect costs Patients with anxiety disorder 5 times more likely to access medical care Slide 40 Anxiety Excessive Worry Associated physical symptoms Avoidant Behavior Unknown internal source vs. known external source Sense of dread Heightened apprehension Slide 41 Causes of Anxiety Psychological Theories Freud: anxiety is a signal to the ego that an unacceptable drive is pressing for conscious representation Behavioral Theories Anxiety is a conditioned response to a specific environmental stimuli Biological Theories Neurotransmitter dysregulation Slide 42 Anxiety Disorder Sub-Types Panic Disorder Generalized Anxiety Post Traumatic Stress Disorder Specific Phobias Social Anxiety Disorder (Social Phobia) Obsessive Compulsive Disorder Anxiety Disorder Due to a General Medical Condition Substance Induced Anxiety Disorder Anxiety Disorder NOS Slide 43 Symptoms of Panic Attack Palpitations Sweating Tremor Shortness of Breath Chest pain and discomfort Nausea Dizziness Fear of losing control Fear of dying Slide 44 Panic Disorder Recurrent, unexpected panic attacks Followed by at least one month of: Persistent concern about having more attacks Worry about the implications of the attacks A significant change in behavior related to the attacks Panic Attack A discrete period of intense fear or discomfort associated with multiple physical manifestations developing abruptly and reaching a peak within 10 min Slide 45 Panic Disorder Prevalence: 2% of the population Sex: 1:2 Male to Female Ratio Usual onset early adulthood Attacks usually last a few minutes Associated symptoms of agoraphobia, depression, substance abuse Higher rate of suicide Marital tension, conflict at work, financial difficulties, higher rate of accessing medical care Slide 46 Differential Diagnosis for Panic Disorder Medical Disorders Cardiovascular diseases Pulmonary diseases Neurological diseases Endocrine diseases Drug intoxications Drug withdrawal Mental Disorders Malingering Hypochondriasis Phobias Post traumatic Stress Disorder Slide 47 Treatment Panic Disorder Pharmacotherapy Tricyclics SSRIs Benzodiazepines Cognitive Behavioral Therapy Address patients false beliefs about panic attack Relaxation techniques, gaining sense of control Family Therapy Insight oriented psychodynamic psychotherapy Help patient understand the unconscious meaning of the anxiety Slide 48 Phobias Phobia: irrational fear resulting in a conscious avoidance of the feared object, activity or situation The single most common mental disorders in the US 10-25% of population are afflicted Increased risk for other psychiatric complications including depression and substance abuse Specific: Fear or avoidance of objects or situations other than agoraphobia or social phobia Commonly involves animals, insects, injury or procedures, heights, darkness Slide 49 Phobias Social: Fear of humiliation or embarrassment in either general or specific social situations Commonly involving public speaking, urinating in public restrooms, stage fright Slide 50 Treatment Phobias Specific Phobias Exposure therapy (behavioral therapy) Insight oriented psychotherapy Pharmacotherapy (Benzodiazepines, SSRIs) Social Phobias Psychotherapy (behavioral, cognitive, insight oriented) Pharmacotherapy (Beta Blockers, SSRIs, Benzodiazepines, Buspirone) Slide 51 Obsessive Compulsive Disorder Lifetime prevalence: 2-3% of population 4 th most common psychiatric disorder Men = Women Mean age of onset 20 years old 2/3 of cases onset before age of 25 years old Can occur in childhood; has been seen in 2 year olds Single more affected than married Caucasian > African American (access to healthcare) Slide 52 Diagnosis Obsession: A recurrent and intrusive thought, feeling, idea, or sensation Compulsion: A conscious, standardized, recurrent thought or behavior, such as counting, checking, or avoiding Obsessions increase a patients anxiety Compulsions decrease a patients anxiety If resist compulsion, anxiety increases A patient realizes the irrationality of the obsessions Either obsession or compulsion. Over 75% have both Slide 53 Treatment OCD Pharmacotherapy Clomipramine SSRIs Lithium Benzodiazepines Psychotherapy Behavioral therapy (exposure, response and flooding) Other ECT Psychosurgery (cingulotomy) Slide 54 Post Traumatic Stress Disorder Experience an emotional stress of potentially life threatening magnitude that would be traumatic for almost anyone Re-experiencing of the trauma through dreams and waking thoughts Persistent avoidance of reminders of the trauma Numbing of responsiveness to such reminders Persistent hyperarousal Symptoms greater than a month Slide 55 Etiololgy The stressor is the prime causative factor Predisposing vulnerability include presence of childhood trauma, personality disorders, poor social support, genetic vulnerability to psychiatric illness, recent stressful life change, recent excessive alcohol use Slide 56 Treatment PTSD Pharmacotherapy SSRIs Mood Stabilizers Hypnotics Anxiolytics Antipsychotics Psychotherapy Supportive Cognitive Group Family Slide 57 Generalized Anxiety Disorder An excessive and pervasive worry accompanied by a variety of somatic symptoms, that cause significant impairment in social or occupational functioning or marked distress A person finds it difficult to control the anxiety Not due tot eh direct physiological affects of a substance Slide 58 Treatment GAD Pharmacotherapy Benzodiazepines Buspirone Mood Stabilizers Antipsychotics SSRIs SNRIs TCA Psychotherapy Cognitive Behavioral Insight Oriented Supportive Slide 59 Treatment Strategies Anxiety Where to begin? If it works, what next? Length Monitoring Therapy If it doesnt work, what next? Dosing ETOH Switch Diagnosis Therapy Slide 60 Psychotic Disorders Schizophrenia Among top 10 leading cause of disability worldwide in people 15-44 age range WHO Peak onset young adulthood All cultures, all ethnic groups, M = W High Risk of suicide 1/3 attempt Schizoaffective Disorder Brief Psychotic Disorder Schizophreniform Disorder Delusional Disorder Shared Psychotic Disorder Slide 61 Psychotic Disorders Clinical Features Delusions Hallucinations Disorganized Speech Disorganized Behavior Negative Symptoms Affect blunting Alogia Avolition Slide 62 Differential Diagnosis Psychosis Bipolar Disorder Depression Personality Disorder Temporal lobe epilepsy Tumor, Stroke Infectious Disease Autoimmune Disorder Toxic illness Drug Intoxications Alcohol withdrawal Slide 63 Clinical Management Safety Pharmacotherapy Family Therapy Social Skills Training Cognitive Rehabilitation Slide 64 Pharmacotherapy Psychosis First Generation, Traditional, Neuroleptics, Typical Antipsychotics Main Therapeutic Effect by Blocking D2 Receptors Second Generation, Atypical Antipsychotics Blocks D1, D2, 5HT2 Slide 65 Dopamine Pathways Four Well Defined Dopamine Pathways Mesolimbic Mesocortical Nigrostriatal DA and Acetylcholine have a reciprocal relationship Tuberoinfundibular DA and Prolactin have a reciprocal relationship Slide 66 Common Typical Antipsychotics Chlorpromazine (Thorazine) Haloperidol (Haldol) Fluphenazine (Prolixin) Perphenazine (Trilafon) Thiothixene (Navane) Trifluoperazine (Stelazine) Slide 67 Common Atypical Antipsychotics Aripiprazole (Abilify) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon) Paliperidone (Invega) Clozapine (Clozaril) Asenapine (Sapharis) Lurasidone (Latuda) Slide 68 Side Effects with AntiPsychotics Typicals Neurologic EPS, Dystonia, Pseudoparkinsonism, akathesia, Atypicals Metabolic Weight gain, Glucose, Lipids, Tardive Dyskinesia, NMS, Q-T prolongation, Hyperprolactinemia Slide 69 Treating EPS Anticholinergics Benztropine Trihexyphenidyl Antihistaminics Diphenhydramine Dopaminergics Amantadine Beta-Blockers Benzodiazepines Slide 70 Treating EPS Use lowest possible dose Move toward a lower potency antipsychotic Use anticholinergic therapy Use Amantadine, Benzodiazepine, Beta-Blocker Consider Atypical Slide 71 Long Acting Injectable AntiPsychotics Typicals Haloperidol Fluphenazine Atypicals Risperidone Paliperidone Olanzapine Aripiprazole Slide 72 Thank you ! ?s