Presentation on theme: "Anti-depressants vs Placebo Joan R. Shepherd, FNP"— Presentation transcript:
1Anti-depressants vs Placebo Joan R. Shepherd, FNP TIC TACS or TREATMENTAnti-depressants vs PlaceboJoan R. Shepherd, FNP
2ObjectivesEstimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depressionRecognize current standard of care/medications for selected mood disorders
3ObjectivesConsider alternative tools for use in primary or acute care settingACT--Acceptance and Commitment TherapyThought Work--Byron KatieSelf-Coaching Model--Brooke CastilloChange Cycle-- Martha Beck, PhD.
4Higher standard of living than ever before Medical treatmentFoodHousingSanitationMoneyWelfareAccess to educationJusticeTravelEntertainmentCareer opportunities
5Harris, R. 2008. The Happiness Trap, Exisle Pub.Ltd Depression13.1 to 14.2 million American adults in any given year1/10th of the adult population/week32 million (one in five)at some point in their lifeHarris, R The Happiness Trap, Exisle Pub.Ltd
6World Health Organization 4th biggest, costliest most debilitating disease in the worldBy 2020, 2nd biggestHarris, R The Happiness Trap. Exisle Pub. Ltd.
7only 50% of depressed people seek and receive adequate treatment Mostly treated by PCPFitzgerald Health Education Assoc. 2007
8DSM IV Criteria at least 5 symptoms in the same 2-week period Sleep: insomnia or hypersomnia, staying asleep problematicInterest: depressed mood, loss of interest or pleasureGuilt; feelings of worthlessnessEnergy: fatigueConcentration: diminished ability to think or make decisionsAppetite: weight change, loss of food enjoymentPsychomotor: agitation or retardationSuicide: recurrent thoughts of death; passive, without plan
10PCPs will not use a screening tool that’s more than 4 questions long! Sally Miller, PhD. NCNP Conference 2007
11PHQ-2 In the last 2 weeks, have you felt down, depressed, or hopeless? In the last 2 weeks, have you felt little interest or pleasure in doing things?96% Sensitivity, less SpecificityPositive response should lead to PHQ-9:download ataccessed
12Kirsch et al 19981998 analysis of 38 manufacturer-sponsored studies of 3000 depressed patientsPatients did improveThis formed the basis for the claim that anti-depressants work
13Studies Impact?The number of Americans taking anti-depressants doubled in a decade13.3 million in 199627 million in 2005National Patterns in Antidepressant Medication Treatment.Marcus and Olfson, Archives of General Psychiatry, 2005.
14hmmmmmm… Comparing improvement in patients on ADM and placebo… Placebo improved about 75% as much as those on ADMor3/4 of benefit from ADM is placebo
15Clinical trials of antidepressants are difficult to design and conduct. more than half of all recent clinical trials of commonly used antidepressants failed to show statistical superiority for the drug over placebo.This is not necessarily because of the ineffectiveness of the antidepressant, but rather because of an increased response to placebo.Kahn et al 2005
16Symptom SeverityEstimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression
17What affects outcome? Fournier et al 2010 Examined Kirsch and Kahn’s meta-analysesLooked at Baseline symptom severityHamilton Depression Rating Scale
18Hamilton Depression Rating Scale (HDRS) Most widely used clinician-administered depression assessment scale.17- items pertaining to symptoms experienced over the past weekOriginally developed for hospital patientsMany variations since then
19HDRS Scoring 0-7 normal or remission 8-13 mild depression moderate depressionsevere depression> 23 very severe depression
20Placebo WashoutMost trials testing the effectiveness of psychotropic drugs begin with a placebo washout phase.Pill placebo administered in single blind fashionImprovement > 20% excluded from the trial prior to randomization
21Kahn et alHypothetically this technique rids studies of placebo responders before randomization of subjects to drug and placebo groups.In theory, this lowers the level of response to placebo in the study and magnifies the superiority of the response to medication.
22Kahn et alAn analysis of 10 years of research: the washout technique does not do what it was designed to do in antidepressant studies.Within placebo or drug groups neither measures of depression nor dropouts were affected by including a preliminary washout in the design.
23Size MattersKirsch: Only 1 of 35 studies comprised samples with mean baseline HDRS scores lower than 23 (very severe depression)Kahn: Minimum entry score 20 (severe or very severe)
2471% of 503 depressed, treatment-seeking out patients had HDRS scores less than 22 Zimmerman, Posternak, Chelminski. 2002
25Conclusion“The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or non-existent, on average, in patients with mild or moderate symptoms.”Founier et al. Antidepressant Drug Effects and Depression Severity. 2010
26Numbers, pleaseThe minimum baseline HDRS score needed to achieve a clinically meaningful ADM/placebo difference is approximately 28Differences are negligible for lower baseline HDRS scores
27Current Guidelines Provide information and support Build a trusting relationshipExplore treatment optionsInformation appropriate to their level of understanding and range of treatmentsComprehensive written info availableAudio availableNational Guideline Clearinghouse. Depression: the treatment and management of depression in adults. Accessed 9/17/10
28Principles for assessment Comprehensive assessment that does not rely simply on a symptom countConsider degree of functional impairment and/or disability and duration of the episode
29Anti-depressants: Which Ones? “Multiple randomized trials of patients in the primary care setting have found similar efficacy for drug therapy and psychotherapy with no clear predictors of which treatment is best for individual patients.”Up To Date. Initial Treatment of depression in adults. 2010
30ADM: How to Choose?which antidepressant less important than treating patients withmedications that they can toleratesufficient doses to achieve symptom remission
31ADM: How to Choose: What has worked in the past? -if it worked before, try it againPositive response in a first degree relativeLess danger of overdose
32ADM: How to choose?Most psychotropic medications used in the treatment of depression work via manipulating serotonin, norepinephrine, and/or dopamine
33Serotonin“…a chemical of thought, movement and behavior, as well as digestion, ejaculation, and evacuation.The body’s all-purpose neurotransmitter, involved in sleep, mood, appetite…”Hanson, D The Chemical Carousel
34Norepinephrine The ‘engergizer’, associated with focused attention Motivation to win a rewardResponsible for the “adrenaline surge”It is the brain’s “go” signalAlso important in memory
35Dopamine “Pleasure chemical” Linked to experiences of joy Attention, movement, problem solving, anticipation of a rewardCreates the desire to repeat a pleasant experienceHanson, 2008.
39Differences among SSRIs… Fluoxetine long half-lifeLess controlTakes longer to be eliminatedIf patient discontinues drug, less likely to have side effectsMinimizes withdrawalPoor compliance, misses doses
40SSRI Differences Paroxetine Drug holiday for sexual side effects bc relatively short 1/2 lifeBetter controlPatient with better compliance
41Adverse Effects: Maximize! SE from agitating to sedatingFluoxetine: energizing and long actingDepressed patient without energyVegetative patientNot for the very anxious patientParoxetine: sedating and short actingUse in patient with depression w/insomniaHigh discontinuation from SE
42Others?Intangible…some patients just do better with one than another for no apparent reason…SertralinePost MI anhedoniaLower SE profilePre-menstrual dysphoric disorder
43Citalopram Escitalopram Substrate cytochrome P450 Mildly sedating Good SE profile
45SSRI Common adverse effects HeadacheUsually controlled with acetaminophenKeep well hydratedMay take 3-4 weeks to resolve
46SSRI Common side effects Associated with increased risk of bleeding, esp in older people or people taking other drugs that have potential to damage the GI mucosa or interfere with clottingConsider adding gastroprotective drug if on NSAID or ASA
47SSRIs-Class Effects GI disturbance-often loose stools Nausea Take with foodExcept paroxetine bc of anti-cholingergic effectSertraline-lose 1/3 dose effect on empty stomachNauseaTake with food and adequate waterUse at bedtimeConsider adding short course of ranitidine (H2RA…not Tagamet)May take 3-4 weeks to resolve
48SSRI Side Effects Weight gain after several weeks Initially mild anorexiaMay lower seizure thresholdNot usually clinically significant at normal dosesBut consider other meds that may have same effect
49SSRI side effects Agitation Reduce the dose by 25% and gradually reintroduceTrazaodone great for helping with sleepSedating antidepressantLow abuse potentialOnset of action = 1/2 - 1 hrPeaks 2-3 hrFull stomach will delay effect
50SSRIsFluoxetine, fluvoxamine and paroxetine associated with a higher propensity for drug interactions than other SSRIsParoxetine is associated with higher incidence of discontinuation symptoms than other SSRIs
51*LOW SODIUM*At the end of the presentation, a NP-PhD in psych approached me and told me I should share with the group that SSRIs can cause low sodium!I hadn’t heard that before…so please take note. Could be extremely important especially in the depressed population!
52When effective?Try a medication for 4-6 weeks for beginning to see a responseTrial of 3 months necessary for true responseThen try another SSRIIn 6 months, go to different class (SNRI, TCA…)
53SNRIs Target norepinephrine (NE) and serotonin 2nd line agents, depending upon co-morbidities and symptom presentationTry for SSRI resistant depression
54Venlafaxine Dose dependent Higher dose, higher BP Consider for patient who presents with depression and chronic painMenopausal symptoms-low doseSallly Miller, PhD. NCNP Conference. 2007
55Venlafaxine Greatest suicide risk of SNRIs more likely to cause side effects that will cause patient to stop taking the medConsider increasing the doses graduallyHigher doses can exacerbate cardiac arrhythmias
56Duloxetine NE slightly lower doses Diabetic peripheral neuropathy Urinary incontinence?
57Desvenlafaxine Active metabolite of venlafaxine Approved for MDD May cause more nausea, HTNMay give with or w/o foodDon’t divide, crush, chew or dissolveMatrix tablet-may see ‘ghost tablet’ in stoolCost for 30 days: $108.71Prescriber’s Letter. Detail Document # Accessed 9/18/10
58Bupropion Inhibits re-uptake of NE, dopamine Very activating Contraindicated in patients with or at an increased risk of seizuresSlight risk of arrhythmias
59Mirtazapine-RemeronNoradrenergic antagonist-blocks presynaptic alpha-adrenergic 5HT2Mildly anti-cholingergicLots of sedationWeight gainGreat GI profile
60Trazodone-Desyrel Good for anxious depression Very sedating ‘Anxiety receptor site’Blocks 5-HT2A, inhibits reuptake of 5-HT
64SuicidalityOne of the main reasons TCAs are used less frequently now than SSRIs is because of how fatal they are in overdose.Thanks to the NP, PhD in psych who approached me after the talk to remind me of this fact! (Sorry, I don’t remember your name!).
66Tricyclics-unapproved but common uses Amitriptyline commonly used for bulimia nervosa and neuralgiasNorpramine-bulimia, panic disorder, premenstrual syndromeContraindicated in acute recovery post MIProlongation of QRS or QT and high doses
67Common uses…Doxepin-depression and/or anxiety associated with alcoholismPamelor-smoking cessation
68Treatment Resistant Depression Response: 50% reduction in symptomsRemission: almost complete absence of symptoms8 week clinical trials only 35-40% achieve remissionGoal: RemissionPrescriber’s Letter Detail Document , accessed
69Strategies: Dosage increase Switching antidepressant Combining antidepressantsAugmentation with non-antidepressant
70Assessing Response Earliest: Increased interest and pleasure in activitiesImprovements in psychomotor retardation3-4 weeks with no response or 6 weeks with partial response despite adherence, consider diagnosis reassessment or change therapy
71Dose Optimization Increase dose if tolerated Esp for partial respondersConsider after 2 weeksIf no response, consider med change
72Switching ADM4-8 weeks after dose optimization with no response or partial responseAchieves remission about 25% timeCan stay in the same class
73STAR*D TrialPatients who didn’t respond to citalopram were just as likely to respond to sertraline as as to extended release venlafaxine or sr bupropion
74Taper paroxetine and venlafaxine to prevent withdrawal Fluoxetine-consider a 4-7 day washout when switching due to long T-1/2Failing two SSRIs, consider a different classConsider co-morbiditiesPain-SNRI or TCAAnxiety, agitation, insomnia-mirtazapineSSRI induced sexual SE-add bupropion, mirtazapine
75Combining Antidepressants Avoids risk of withdrawal symptoms and loss of benefit from 1st ADMDrug 2 may counteract Drug 1’s SesMost common combo is Bupropion plus SSRISSRI plus TCAKeep TCA low range (25-75mg) bc SSRI can increase TCA levels
76Combining ADMsTrazodone (Desyrel) mg plus SSRI or venlafaxine for sedating effectTrazadone plus fluoxetine or paroxetine can inhibit the elimination of trazodone’s metabolite, leading to CNS stimulation
77Combining ADMsMirtazapine/SSRI, bupropion, or venlafaxine has showed improvementLittle dataConsider for patients with nervousness, insomnia or sexual side effects
78MAOI’sCombinations can cause life threatening serotonin syndrome or hypertensive crisisLeave to the specialists!
79Data does NOT support combining venlafaxine with other SSRIs Or combining two SSRIs.
80Augmentation with Non-ADM Treat concomitant conditionsImprove specific symptomsQuick onset of other medsBuspirone (BuSpar)Improves SSRI-induced sexual SesGood choice for depressed patients with anxiety
81Aumentation with non-ADM Atypical AntipsychoticsUsed with SSRI improve NE and serotonin release through blockade of 5-HT2A receptorsImprovements in sexual function and sleepLikely effective at lower doses than schizophrenia, minimizing SEs
82Augmentation with Atypical Antipsychotics Aripiprazole (Abilify)-add-on treatment for MDD in adultsStarting dose when adding to ADM is 2-5mgCan increase by 2-5mg weeklyMaximum 15mg/daySE: akathisia, restlessness, insomniaMay help to add mirtazapine for akathisia
83Symbyax-combination fluoxetine/olanzapine treatment of bipolar depression and derpession in patients who have failed 2 ADM of sufficient dose and durationStarting dose 6/25 QHSCaution: hypotension, hepatic impairmentMost common adverse effects:Weight gainIncreased appetiteDry mouthSonmolenceFatigue
84Quetiapine (Seroquel, Seroquel XR) Treatment resistant depressionDose qhs50mg day one and two, then 150mg dailyWatch lipids, weight gain, diabetes, tardive dyskinesia!Use lowest effective dose for shortest durationWhen switching, start Seroquel XR while tapering ADM
85Atypical Antipsychotics Glucose monitoringCheck fasting glucose in patients who develop symptoms of dibetesBaseline fasting glucosePeriodically in patients with risk factorsMetabolic effectsRisk of sudden cardiac deathBlack box warning re Suicidality
86Augmentation con’t Risperdal and Geodon also being studied Lamotrigine (Lamictal) mood stabilizerimproves several symptoms of depression:Mood, lack of interest, decreased energy, impaired cognitionSE: dizziness, headache, nausea, sleepinessLike lithium, may be good adjunct for patients with bipolar
87Lithium Improves depression with poor response to TCIs Efficacy with SSRIs not so good-both serotonergicSerum concentration monitoringAdverse effects (weight gain, tremor)Serotonin syndrome
8871% of 503 depressed, treatment-seeking out patients had HDRS scores less than 22 Zimmerman, Posternak, Chelminski. 2002
89Depression is never an accident; it is perfectly designed to tell you something important about how your life is going.
90Therapeutic listening skills…. Tools to take home!
91Thought Work Acceptance and Commitment Therapy Byron Katie Brooke CastilleMartha Beck, PhD.
92Thought WorkThe technique of stepping back, becoming the Compassionate Watcher of my thoughts.Becoming aware of the stories I am Telling Myself.Realizing: I am a Person who has thoughts…I am not my thoughts.
93Acceptance and Commitment Therapy Grew out of Cognitive Behavioral TherapyExamines the role of language and thoughts in sufferingBased on the assumption that most unwanted internal experiences cannot be eliminated or controlled, so they must be accepted.
94Valued Actions Heavy emphasis on values-based living Knowing one’s sense of direction dignifies one’s experiences
95Lizard Fears Human brain evolved for survival Lack or Attack fears Lack: Not enough food, water, shelter, sexAttack: saber toothed tigers
96Top 10 Lizard Tunes Write them down Put them to music Twinkle twinkle Happy birthday
98Self-Coaching Model Brooke Castillo Circumstances: things that happen in the world, factsThoughts: things that happen in your mindFeelings:not physical sensations, but emotional feelings in your bodyActions: what we DO in the worldResults: what we see in the world, the effect of our action
99Circumstance:57 yoAAf hx of HTN. Flat affect and various somatic complaints. Recent change in job responsibilities from working night shift in laundry room to more physical house-keeping.Thought:Evening shift people are slobs, they leave this place a mess, making my job so much harder. My supervisor doesn’t care…
100SC 101 Feelings: anger, frustration, victimized, powerless Actions: work with hostility, isolate from other workers, avoid supervisorResults: HTN increased, insomnia, dreads going to work, angry at home.
101Being in the place of the watcher. How are you reacting to your thoughts?How can you change your thoughts?Thoughts cause Feelings and you can change your thoughts.Regardless of circumstances, you can always change the thoughts.
102The result of your actions caused by your feelings will always prove the original thought….brains compelled to gather evidence to support the original thought.
103Result: HTN increased, insomnia, dreads going to work, angry at home. Will always prove the original thought:“This job is killing me…The evening shift people are slobs. They leave this place a mess, making my job harder…my supervisor doesn’t care…”
104Intervene at level of THOUGHT. Notice your thoughts about the circumstance.Change the thought to something that feels slightly better, or flip it around.This will give you the power to change your feeling about the circumstances.
105In the moment of asking, “what am I thinking In the moment of asking, “what am I thinking?” you assume the position of the watcher.This process alone can create new wiring, allows a person to make conscious decisions and a feeling of control.
106How to change the thought? a full thought turnaroundslightly better thoughtWrite down the painful thoughtWrite down the feeling the thought is causingTry to find a slightly better-feeling-thought you know is true…
107they’re sloppiness is job security for me Maybe the shift before them left them a messI can ask my supervisor to keep me in mind the next time there’s an openingIt’s kind of satisfying to make the room look niceI’m getting a little exerciseI can imagine that it’s my Mother’s room in her nursing home
108SC 101 Example 2 24 yocm recently completed detox from methadone Circumstance: No GFThought: I deserve one. Look at all the losers with GFs. I can’t get one.Feelings: loneliness, frustration, desperateActions: Passing cards out to people with his number. Avoiding actually speaking to girls. Watching others with contempt.Result: No GF. Depressed, isolating.
109Change the ThoughtNew Thought: It’s highly likely I’m going to meet girls now that I’m in recovery. I’ve got a lot more to offer.Feelings: hopeful, peaceful, less desperateActions: discuss with counselor, observe relationships that seem to be working, read helpful books. Focus on your recoveryResult: more confidence, willing to speak to a girls without expectations of liason
110Thought Work or Inquiry Byron Katie Suffering ThoughtIs it true?Can you absolutely know it’s true?How do you react when you think this thought?Who would you be without the thought?Turnaround
111Inquiry/The Work36 yoAAm incarcerated 8 years. Productive Citizen class, be out in next couple months. Resentments.Painful Thought: My mother shouldn’t have given me awayIs that true?Can you absolutely know it’s true?She couldn’t care for me
112Who would I be without this thought? Believe a woman could love and stay with meNot feel so angry toward my motherBuild a relationship with her
113Turnaround: Opposite, Self, Others 1. My mother should have given me awayCouldn’t care for meGreat act of loveOpened doors for me2. I shouldn’t have given myself awaybetrayed myself, not honoring myself,ending up in prison
1143. I shouldn’t have given my mother away: I’ve given away my relationship with her because I’ve been so hurt and angry
11538 yo morbidly obese cf chronic lymphedema, depression, anxiety 38 yo morbidly obese cf chronic lymphedema, depression, anxiety. Years earlier had witnessed her mother’s death after long illness.
116Limiting Belief/Painful Thought: “I wasn’t there for my mother.” Is that true?well…2. Can you absolutely know it’s true?3 reasons why it might NOT be true-sat up together many nights talking, laughing-put off going to college-responsible for her meds
1173. How do I react when I’m having this thought? -stuck-undeserving-sad, trapped4. Who would I be without this thought?-free-light-making plans for school
118Turnaround statement: 1. Opposite: I was there for my mother.2. Self: I wasn’t there for me.3. Other: My mother wasn’t there for me.Provide evidence for each statement, without forcing it.Is there a thought that is more true for you?
12148 yocf in long term relationship presents with somatic complaints 48 yocf in long term relationship presents with somatic complaints. Feeling ‘out of sorts’, distracted, sleeping problems. Little interest and pleasure in doing things. Recently paid off mortgage.
122Catalytic Event: Joyful event/transition Paying off the mortgage threw her into Square One.Redefinition of self. Not the “starving artist” anymore.Look at the story, look at the thoughts.May need to go through a grieving process.
12456 yocm was a body builder by hobby 56 yocm was a body builder by hobby. Seven years earlier severely injured his back while working out. Had surgery and was on daily high dose opiates til he came for AOD.Felt great physically, but at 1 month f/u stated he’d “never been more depressed in his entire life”.
125Catalytic Event: Back Injury, traumatic event threw him into the Change Cycle. Had not gone through a grieving process to allow transition into square 2: Dream and Scheme.Follow up visit 1 month-making plans to return to school. Family life much improved.
126Depression is never an accident; it is perfectly designed to tell you something important about how your life is going.
129Beck, Martha. Life Coach Training Handbook. 2008. Castillo, Brooke. Self-Coaching 101,Fournier, DeRubeis et al. Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta- analysis. JAMA 2010; 303 (1):47-53Hamilton MA. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.Hyman, Mark. “Why Antidepressants Don’t Work for Treating Depression”
130Katie, Byron Kathleen. http://www.thework.com/index.php Lee S, Walker JR, Jakul L, Sexton K. Does elimination of placebo responders in a placebo run-in increase the treament effect in randomized clinical trials? A meta-analytic evaluation. Depress Anxiety. 2004; 19(1):10-19.National Guideline Clearing House, Depression. The treatment and management of depression in adults
131Strosahl, K. and Robinson, P. The. Mindfulness. and Acceptance Strosahl, K.and Robinson, P. The Mindfulness and Acceptance Workbook for Depression, 2008.