Management of Clients with Depression:

Management of Clients with Mood Disorders:A Practical ApproachBrenda Patzel PhD, APRN 1DEPRESSION MANAGEMENT2What have you seen in practice and how common is depression? In the community 2 -4%In primary care 5-10%Medical inpatients 14%

We know anecdotally that depression is endemic in our society today.Studies have estimated that major depression occurs in 2%4% of persons in the community, in 5%10% of primary care patients, and 10%14% of medical inpatients.

In each setting there are two to three times as many persons with depressive symptoms that fall short of major depression criteria. Recent studies have found that in one-third to one-half of patients with major depression, the symptoms persist over a 6-month to one-year 3 Incidence of major depression: Life time occurrence: 20% for Women 12% for MenLess common in the Black populationIncreased with advancing ageAssociated with increasing medical illness and institutionalization

Any ideas why? 4

Risks of untreated or undertreated depression:Depression is associated with: Heart diseaseDiabetesSuicide

Psychosom Med. 2001 Jul-Aug;63(4):619-30.Association of depression and diabetes complications: a meta-analysis.de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ.

5Criteria for Diagnosis of Major Depressive Disorder: DSM-IV TRAt least 5 of the following over 2 week time period that represent a change from previous level of functioning.Depressed moodDiminished interest or pleasureSignificant weight loss or gainInsomnia or hypersomniaPsychomotor agitation or retardationFatigue or loss of energyDecreased ability to concentrate; indecisivenessRecurrent thoughts of death and/or suicide

6Symptoms do not meet criteria for Mixed episode.

Cause clinical significant distress and impaired functioning.

Are not due to a direct physiologic effect, substance or general medical condition.

Symptoms are not better accounted for by bereavement.

Symptom last longer than 2 months or are characterized by functional impairment, worthiness, suicidal ideation psychotic symptoms psychomotor retardation.7Underlying PathophysiologyNot clearly definedClinical and pre clinical trials suggest disturbances in monoamines ( Serotonin (5HT), Norepinephrine (NE), Dopamine (DA)Clinical experience indicates complex interaction between neurotransmitter availability, receptor regulation and sensitivity and affective symptoms.

8Theoretically Depression is the Result of:Inefficient or dysfunctional projections of Serotonin (5HT)Norepinephrine (NE)Dopamine (DA) Into the Amygdala and Ventromedial Prefrontal Cortex .

VMPFCAmygdala Malfunctioning of certain brain regions manifesting as either hypo or hyperactivity may hypothetically be altered dur to aberrant neuronal activity and information processing, leading to the different presenting symptoms of depression.9Sleep DisturbancesHypoactivation of 5HT, NE, and DAProjections from brainstem nuclei to hypothalamus, thalmus, basal forebrain and prefrontal cortex hypothetically are involved in sleep disturbances

ThalamusHypothalmausPFCBFB10 Guilt/Worthlessness- 5HT projections to the amygdala and the ventromedial prefrontal cortex as part of the emotional brain is thought to effect these. -Projections into the orbital frontal cortex is hypothetically involved in suicide.

OFCVMPFCAmgdala11Theoretical effect of antidepressant actions.Act to normalize the levels of three neurotransmitters By blocking presynaptic monoamine transporters (reuptake pumps)Antagonist activity at presynaptic inhibitory receptor sites, enhancing neurotransmitter release.Inhibition of monoamine oxidase, reducing neurotransmitter breakdown. Support for these theories can be found in clinical experience can be seen with drugs that produce only an acute rise in neurotransmitter availability, such as cocaine and do not have the efficacy over time that antidepressants do. Exposure is necessary to produce a change in symptoms. Together with preclinical research findings, a role for neuronal receptor regulation overt time in response to enhanced neurotransmitter availability.12

Differential Diagnosis-Medical considerations:Mood disorders secondary to CNS conditions and DiseasesInflammatory conditionsSleep disordersEndocrine disordersInfectious processesPharmacologic agentsMood disorders secondary to CNS conditions and Diseases:Organic syndromes. Alzheimer disease, Parkinson's, Huntington disease, MS, stroke, seizure disorders

Inflammatory conditions Lupus,

Sleep disorders- obstructive sleep apnea pt.s partner report , daytime sleepiness, snoring sleep studies

Endocrine disorder s- hypothalamic-pituitary adrenal axis or thyroid. i.e. Addison, Cushing, hyper and hypothyroidism prolactinomas, hyperparathyroidism

Infectious processes syphilis, Lyme disease, HIV encephalopathy

Pharmacologic agents- antihypertensives, beta blockers, reserpoine, ethyldopa calcium channel blockersSteroids, Estrogens, progesterone, testosterone gondadotropin-releasing hormone antagonist Rx that effect sex hormonesH2 blockers ranitidine, cimetidine sedativesMuscle relaxants,Appetite suppressantsChemotherapy agents,interferon

13Differential Diagnosis Psychiatric considerations:Substance use, abuse, dependenceSeasonal affective disorderDysthymiaAnxiety disordersEating DisordersOther psychiatric disordersSubstance use, abuse, dependenceSignificant mood symptoms, especially with ETOH, cocaine, amphetamines, marijuana, sedatives and narcotics. Inhalant abuse young male pts in particularSeasonal affective disorder- seasonal pattern treated with bright light therapy with or without light therapyDysthymia symptoms of depression low mood primary symptoms may be before MDDO present for at least 2 yearsAnxiety disorders- higher risk for developing co morbid depression.Eating Disorders-Other psychiatric disorders Personality disorders e.g. borderline personality disorder mood changes prominent symptom Hard to differentiate when present with depressed mood as many clients appear as labile, demanding, pr pathologically dependent and may look different after treatment.

14AssessmentAppearance and Affect - hygiene, slowing or increase in motor activityMood and Thought Process- dysphoria, irritability, mood swings, anhedonia, worthlessness, hopelessness, helplessnessPsychosis rule out history of bipolar disorder, schizophrenia, schizoaffective disorder, substance abuse or organic brain syndrome.expressed as sadness, heaviness15Cognition and Sensorium- Poor memory and concentration. Most commonly no deficits.

Speech Normal, slow, monotonic, or lacking in spontaneity and content. Pressured speech racing thoughts -think mania. Disorganized think psychosis

Thought content Consistent with dysphoric moodAssess for hopelessness, suicidal ideation or thoughts of harm towards others.

History of suicide attempt or violence -Should be noted. Hallucinations and Delusions- command hallucinations, somatic delusions.

16Depression Screening Tests Examples Mood Disorder Questionnaire PHQ-2 and PHQ-9

PHQ- 2 and PHQ-9 Available from : http://www.phqscreeners.com/terms.aspxTools and Scoring;

http://www.cqaimh.org/tool_depscreen.html

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The PHQ2 includes the first two items of the PHQ-9 and inquires about the frequency of depressed mood and Anhedonia over the past two weeks. The purpose of the PHQ2 is not to establish a final diagnosis or to monitor depression severity but rather to screen for depression as a first step approach.

Scores range from 0-6

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The PHQ-9 includes the diagnostic criteria from the DSMIVtr with other leading major depressive symptoms into a brief self-report tool.The tool rates frequency of symptoms which facto into the scoring of severity index.Question 9 screens for suicidal ideation.

Follow up questions assign weight.Scoring 19Scoring: 5-9 Minimal SymptomsSupport/educate; Call, Re-check10-14 Minor depression Support, watch Dysthymia, or mild MDD Treat

15-19MDD, moderately severe Treat

>20MDD, severe Treat

For Depression diagsnosis:

Questions 1 and 2 need to be a 2 or 3

Questions 1 -9

Questions 1-8 endorsed as 2 or 3Question 9 as 1, 2, or 3

Endorsed as somewhat difficult or very difficult or extremely difficult

Add the total points for each column 2-4 separately

The total score gives the severity score20PHQ-2 is a first step approach It includes the first two items for the PHQ-9.

Patients who test positive for the PHQ-2 should be further evaluated by the PHQ-9, other diagnostic tests in addition to a direct interview.

Screener OverviewRecognizing signs of mental health disorders is not always easy. The Patient Health Questionnaire (PHQ) is a diagnostic tool for mental health disorders used by health care professionals that is quick and easy for patients to complete. In the mid-1990s, Robert L. Spitzer, MD, Janet B.W. Williams, DSW, and Kurt Kroenke, MD, and colleagues at Columbia University developed the Primary Care Evaluation of Mental Disorders (PRIME-MD), a diagnostic tool containing modules on 12 different mental health disorders. They worked in collaboration with researchers at the Regenstrief Institute at Indiana University and with the support of an educational grant from Pfizer Inc. During the development of PRIME-MD, Drs. Spitzer, Williams and Kroenke, created the PHQ and GAD-7 screeners.

21ANTIDEPRESSANTSSSRIsSNRIsAtypical Antidepressants

CLASSIC ANTIDEPRESSANTSTricyclic (TCAs)MAOI

22SSRIs: Selective Serotonin Act by inhibiting the reuptake of serotonin.All have different secondary pharmacological actions Various degrees of SNRI and DNRI effectsVarying degrees of CYP 450 effectsFluoxetine ( Prozac) very long half lifeParoxetine (Paxil) anticholinergic effects good for anxiety; some weak NE effect potent CYP45o inhibitor effects; rapid metabolism problems with discontinuation; sexual dysfunction.Sertraline (Zoloft) acts as dopamine reuptake inhibitor as well; other actions may contribute to anxiolytic effect; may be useful in psychotic depression 23SSRIs ContinuedFluvoxamine (Luvox)- efficacy as an anxiolytic; psychotic depression; OCDCitalopram (Celexa) has a mild antihistamine effect; well tolerated by elderly patients; at lowest dose is inconsistent in therapeutic action requiring increase I dose for effectiveness unfortunately now not to exceed 40mg.Escitalopram (Lexapro)- lowest dose may be more effective; better tolerated with the fewest CYP450 drug reactions.24SNRIs: Serotonin Norepinephrine Reuptake InhibitorsAct on both serotonin and norepinephrine in the prefrontal cortex.Venlafaxine (Effexor)- norepinephrine varies by dose but serotonin is moderately present at all doses; may have discontinuation problems; time released better tolerated.Desvenlafaxine (Pristiq)-greater norepinephrine effect than serotonin; tested for perimenopause effect with good results.Duloxetine (Cymbalta) approved for neuropathic pain; useful for painful physical symptoms of depression; for geriatric depression with concurrent cognitive effects; CYP450 inhibitor, numerous drug interactions needs close monitoring; difficult to treat patients may use higher dose as well as twice a day dosing.25Atypical AntidepressantsBupropion (Wellbutrin)- An NDRI; low levels of NE combined with DA; effect on Striatum and nucleus accumbens useful for cravings (e.g. nicotine withdrawal); stimulating; no sexual dysfunction; contraindicated for patients with a history of seizures Mirtazapine (Remeron) potent 5-Ht2, 5-HT3, alpha-2 receptors result in higher levels of serotonin and NE; very sedating; adverse effects of drowsiness and weight gain improves over time; may have some anxiolytic effect. Trazodone (Desyrel)- very sedating; more often used for sleep than depression.26TCAs :Tricyclic Antidepressants TCAs include: amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin), clomipramine (Anafranil), doxepin (Sinequan), imipramine (Tofranil)Used less commonly nowAdvantage is low costDisadvantages considered to be most lethal in overdose; narrow therapeutic windowAdverse effects- anticholinergic and antihistaminic properties include sedation, confusion, dry mouth, constipation, sexual dysfunction, weight gain, cardiac/conduction effectsNot considered for first-line treatment27MAOIsEffective in broad range of affective and anxiety disordersRisk of hypertensive crisis patients must maintain diet low in tyramine. Multiple drug interactionsSeldom currently used as monotherapy; not considered for first-line treatment28Treatment Strategies for Treatment Resistant DepressionUnder use of medication Under treatmentNon-adherenceAdding another antidepressant to augment current treatment Consider mechanism of actionRetest29Treatment Strategies for Treatment-Resistant DepressionAdding another classification of medication to augmentAntipsychoticsAbilifySeroquel Other medications

30Treatment Strategies for Treatment-Resistant DepressionRefer for therapy increases efficacy of treatment Consult or refer if options are exhausted or anytime if beyond comfort levelSuicidal IdeationManiaPsychosisContinued worsening of depression and compromised health

31Possible Complications for Patients Receiving Antidepressant TherapySuicidal Ideation Black Box Warning Mania activation- patients with bipolar disorder may initially present with unipolar depression.Serotonin SyndromeAlterations in lab valuesNaClotting time for patients on some anti-clotting medicationOsteoporosis Sexual Dysfunction

32BIPOLAR DISORDERApproximately 20%-30% of patients in the primary care setting have bipolar disorder, yet it remains underrecognized and undertreated33OverviewPreviously named Manic Depressive D.O.Thought to be rare with one basic set of symptomologyNow seen as a spectrum of conditionsQuite common possibly effecting 2.2 million American Adults

34Bipolar Disorder SpectrumConsidered to be poles between depression and maniaVarious forms of the disordersBipolar IBipolar IIHypomaniaCyclothymia35

Depressed NormalManic MOOD RANGEHypomanicDepressedBipolar DisorderMajor DepressionDysthymiaCyclothymiaElation36CriteriaThree or more of the following(four if mood is only irritable):Inflated self-esteem or grandiosityDecreased need for sleepHyperverbal, pressured speechFlight of ideas, racing thoughtsDistractibilityIncrease in goal directed activitiesMaybe irritable short tempered

37Criteria continued:Excessive involvement in:buying sprees sexual indiscretionsbusiness investments38Excessive involvement in pleasurable activities that have a high potential for painful consequences: buying sprees, sexual indiscretions, business investments

Bipolar disorder is further characterized by number of manic episodes, as well as most recent and current episode.Rapid cycling: 4 or more/yearSingle most effective treatment stop antidepressant39Underlying PathophysiologyNot clearly definedMonoamines ( Serotonin (5HT), Norepinephrine (NE), Dopamine (DA) are implicated in both the symptoms as well as the treatment of mood disorders.Associated with inefficient processing in various brain circuits and functioning that is out of tune.Clinical experience indicates complex interaction between neurotransmitter availability, receptor regulation and sensitivity and affective symptoms.

40Theoretically symptoms of Mania are the Result of Malfunctioning Brain Circuits:Hyperactive NE, 5Ht, DA Projections Inefficient processing and hyperactivity in the Amgdala,Ventromedial Prefrontal Cortex and Orbital Frontal Cortex

VMPFCO F CElevated/Expansive and Irritable Mood 41Mania SymptomsContinued:Grandiosity, Flight of ideas, Racing thoughts Related to inefficient information processing from hyperactivity in the Nucleus Accumbens. Hyperactive DA and 5HT

Risk taking & Pressured Speech Orbital Frontal Cortex; Dorsolateral Prefrontal Cortex & Ventromedial Prefrontal Cortex- 5HT DA and NE

VMPFCO F CDLPFC Some of the same brain regions associated with psychosis May have manifestations of poor impulse control 42Mania SymptomsContinued:SLEEP CIRUCITSDecreased need for sleep may be linked to inefficient information processing in the Hypothalamus, Thalamus and Basal Forebrain. Hyperactive 5HT, DA and NE

BFThalamusHypothalamusDecreased subjective need for sleep43Mania SymptomsContinued:DISTRACTABILITY/CONCENTRATIONAberrant Information processing in the Dorsolateral Prefrontal Cortex related to Hyperactive DA and NEGOAL DIRECTED ACTIVITY OR AGITATIONInefficient information processing in the Striatum Hyperactivity of 5HT and DA

DLPFCStriatumCognitive problems in mania poor concentration and distractibility

44Presentation in Primary CareDepressionMoodswingsDifficulty sleepingIrritabilityFatigueIn ability to focus and concentrateETOH problemsSTDsSocial consequences of their illness45CARDINAL SYMPTOMS OF BIPOLAR DIORDERManic Mood and Behavior Euphoria, grandiosity, pressured speech, impulsivity, excessive libido, recklessness, social impulsiveness, diminished need for sleepDysphoric or Negative Mood and Behavior Depression, anxiety, irritability, hostility, violence or suicidePsychiatric Symptoms Delusions and hallucinationsCognitive Symptoms Racing thoughts, distractibility, disorganization, The most common symptoms are depressionWith Mixed episodes most dysphoria experiencing severity. Patients feel hopeless and depressed but also have significant energy greatest risk for suicide. ETOH further increases risk.46COMORBIDITIESPSYCHIATRIC: Anxiety disorders (92.9%); Substance abuse 71%; Conduct disorder; ADHD; Substance AbuseMEDICAL: Migraines, Thyroid disease, Hypertension, COPD, AsthmaSubstance abuse 46% with clients with Bipolar D.O vs. depressed clients 21%47MisdiagnosisMajor DepressionPersonality DisorderPost Partum Depression

Frequently misdiagnosed some patients sought treatment for 20 years before diagnosisMisdiagnoses has significant impact on pt. lives. Inadequate treatment perpetuates the symtpoms of biplar disorder with negative consequences for he course and outome of the illness and pt. quality of life.The symptoms of bipolar disorder may worsen overtime in the absent of proper treatment. Are at more risk for suicideOrganic chagnes to the brain with repeated manic episodes.48Detecting Bipolar D.O. - DIGFASTD = DISTRACTIBILITYI = INDISCRETION OR DISINHIBITIONG = GRANDIOSITYF = FLIGHT OF IDEASA = ACTIVITY INCREASES = SLEEP DEFICIT OR DECREASED NEED FOR SLEEPT = TALKATIVENESS49MOOD DIORDER QUESTIONAIRE (MDQ)Brief patient self report covering 13 different manic symptoms which patients record as yes or no.Seven or more positive responses on the MDQ indicate the presence of concurrent manic symptoms and a moderate level of impairment. Highly suggestive of bipolar illness.Available:http://www.dbsalliance.org/pdfs/MDQ.pdf

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51Key Factors in Diagnosis BDOAge of onsetFamily historyPresence of mania or hypomaniaCycling of moodResponse to treatment antidepressants 52Treatment-MOOD STABILIZERSLithium (LiCO3) A Salt. Mechanism of action not well understood. Effects intracellular CA, also interacts with DA, NE and 5-HT. Has Narrow Therapeutic Window Level generally .5-1.5mEq/L (At 1.5 mEq/L is approaching toxic) Has proven efficacy in Mania. Not effective rapid cycling.Depakote (valproate )- May act by decreasing excessive neuron transmission and decrease of ions through voltage sensitive sodium channels and decrease excitatory nerotransmissions. HEPATOTOXICITY

Lithium may effect second messenger enzymes and modulation of g proteins. Effecting downstream signal transductionNonsedating and nonaddictiveEarly side effects disappear after 4 weeks.

Both require blood draws to manage53Lamictal (Lamotrigine) Prevention of recurrence of both mania and depression.Not approved for treatment of bipolar mania. May act by reducing release of excitatory neurotransmitter glutamate. STEVEN JOHSON SYNDROME

54THESE ATYPICAL ANTIPSYCHOTICSALSO HAVE FDA APPROVAL TO TREAT BIPOLAR DISORDER:*SEROQUEL XR (quetiapine)- Manic/mixed (400-800mg) and Bipolar Depression (300mg)ABILIFY (aripiprazole) - Manic/mixed(15 -30mg) and Major Depression Adjunct (2-15mg)RISPERDAL (risperidone) - Manic/mixed*GEODON (ziprasidone) - Manic/mixedSAPHRIS (asenapine) Manic/mixed*Have established efficacy for psychotic mania as well as nonpsychotic mania. Some also have indications as for depression i.e. Seroquel XR;

55RESOURCES FOR PRESCRIBINGPrescribing for Better Outcomes.org

http://www.prescribingforbetteroutcomes.org/files/MAINTENANCE%20TREATMENT%20of%20BPMD%20Revised%20April%2019%202009.pdf 56TREATMENT INSIGHTS:Clients present more often with depression than mania. If bipolar need decision to use atypical antipsychotic or lamictal and avoid antidepressants.If presenting with mild mania consider valproate, lithium, or atypical antipsychotic or combination. For antidepressant induced mania stop the antidepressant.Must consider what presenting problem is and decide whether to treat from top down (antimania) or bottom up (mood stabilizer.)Generally monotherapy is not possible to manage bipolar disorder.Important to know if depressive symptoms depression or bipolar.If presenting with mild mania consider valporoate, lithium, or atypical antipsycotic or combintaiton. In primary care may decide to start with atypical antipsychotic and still avoid antidepressants with referral to a speciaist if this treatment isnt satisfactoy.

57Closing ThoughtsMajor depressive disorder tends to be a recurrent condition (50-80%) warranting long-term use of antidepressants as a preventative therapy.Avoid abrupt discontinuation of medication, taper medication instead.Psychotherapy is an invaluable treatment modality in management of depression.Good follow-up is essential.

58Agency for Healthcare Research and Quality. Comparative Effectiveness of Secon-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. AHRQ: Agency for Healthcare Research and Quality> Available at http://effectivehealtcar.ahrq.gov/healthinfo.cfm?infotype=rr&ProcessID=7%20&DocID=61

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Fournier, J.C., DeRubeis, R.J., Hollon, S.D., Dimidjian, S., Amsterdam, J.D., Shelton, R.C. et al. (2010) Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA, 303, 47-53. Medline.

Lewis, F., Kass, E., & Klien, R. ( 2004). An overview of primary care assessment and management of bipolar disorder . Journal of the American Osteopathic Association. http://www.jaoa.org/content/104/6_suppl/S2.full.pdf Nelson, J.C., Papkostas, G.I., (2009). Atypical antipsychotic augmentation in major depressive disorders: A meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry, 166, 980-91. Medline.

Rush, A.J., Trvedi, M.H. Wisniewski, S.R., Nierenber,g A.A., Stewart, J.W., Warden, D. et al. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163, 1905-17.

59Sansone, R., & Sansone, L. ( 2011). Managing bipolar disorder in the primary care setting: A perspective for Mental Health professional. Innovations in Clinical Neuroscience. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225131/

Suehs, B.T., Argo, T.R., Bendele, S.D., (2008). Texas medication algorithms project procedural manual: Major Depressive Disorder algorithms. Texas Department of State Health Services.http://www.dshs.state.tx.us/mhprograms/disclaimer.shtm.

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Small, G. (2009). Pharmacotherapy and other treatments for elderly patients with depression. JClinPsychlopedia. Retrieved from http://www.cmeinsititute.com/psycholpedia/depression/4dep/sec2/section/aspStahl, S. (2008). Stahls essential psychopharmacology:Neuroscientific basis and practical applications.( 3rd. edition). Cambridge University Press: New York.

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