Mentoring Session: Participant Cases

Transcription

1 Handout for the Neuroscience Education Institute (NEI) online activity: Mentoring Session: Participant Cases

2 The Case: 55-year-old patient with depression and anxiety The Question: What to do when antidepressants stop working? The Dilemma: Treating non-remitting depression and anxiety

3 Patient Intake 55-year-old female with unipolar major depression and anxiety Over the years, her symptoms have waxed and waned and she has been relatively unstable The patient states that her depression started at 4 although she first received medical attention at age 17 At age 17, the patient developed severe panic attacks and was treated with amitriptyline A previous trial of lithium was partially effective but the patient developed intolerable side effects The patient reports that while discontinuing medications (perhaps alprazolam), she may have had 2 seizures; the details are unclear The patient relates to only very short periods of feeling well and states that she has never been normal

4 Patient Intake Medical history is significant for: Grave s disease Endometriosis leading to hysterectomy and oophorectomy at age 48 Gastroesophogeal reflux Hypertension Elevated lipids Family history is significant for: Alcoholic and verbally abusive father Mother with depression All three of the patient s siblings have been treated for depression

5 Current Medications Bupropion (300 mg/day) + Paroxetine (40 mg/day) Does not seem to be as effective as in the past Clonazepam (0.5 mg twice per day) Patient feels this is somewhat effective for her anxiety Buspirone (15 mg twice per day) Patient feels this is ineffective although it has helped some of the patient s relatives Dextroamphetamine (5 mg twice per day) Patient feels this gives her some energy but makes her anxiety slightly worse Thyroid treatment for Grave s disease Estrogen replacement therapy for the past 7 years Ranitidine for gastroesophogeal reflux Diovan for hypertension Lovastatin and Tricor for elevated lipids

6 Pretest Question 1 Of the following choices, what would you do? 1. Another trial of lithium 2. Add L-methylfolate 3. Add modafinil 4. Add an atypical antipsychotic 5. Cease all psychotropic medication and switch to an MAOI 6. Switch to an MAOI while maintaining clonazepam 7. Try a non-pharmacological approach (ECT or TMS)

7 Attending Physician's Mental Notes It may be useful to try and stabilize this patient with a low dose (300 mg twice per day) It is possible that L-methylfolate may help and have few side effects, but it is unlikely to have a dramatic effect Modafinil has been shown to have positive outcomes in patients with bipolar depression Electrical stimulation therapies may also provide some benefit for this patient Given that this patient has had some response to dextroamphetamine, an MAOI may be effective

8 Attending Physician's Mental Notes MAOIs have been shown to be effective for both depression and panic disorder. An MAOI may cause insomnia and agitation, thus worsening this patient s panic attacks. Maintaining (and increasing) concomitant clonazepam dose may be necessary It may also be necessary to augment an MAOI with an atypical antipsychotic, such as quetiapine, at least in the short term Switching to an MAOI will require five days of paroxetine/bupropion washout. Conversely, if the patient needs to switch back to her original treatment, a two week washout period of the MAOI will be necessary Given the patient s possible history of seizures, caution is indicated when altering her treatment regimen

9 Take-Home Points This patient has achieved only partial symptom improvement despite the use of numerous anxiolytics and antidepressants For patients with treatment-resistant depression, it may be necessary to look to both the past (MAOIs) and the future (atypical antipsychotics) in order to achieve optimal outcomes

10 The Case: 41-year-old patient with treatment-resistant depression and insomnia The Question: Can sleeping agents be used in a patient taking an MAOI? The Dilemma: Optimizing outcomes in patients with depression

11 Patient Intake 41-year-old male patient with treatment-resistant depression and a history of drug addiction The patient has been sober for the past 4 years Currently having good response to transdermal selegiline (12mg/24hr)

12 Patient Intake (cont) Chief complaint is insomnia that began shortly after starting transdermal selegiline The patient has difficulty falling asleep until ~4 am every night He awakes at ~6:30 am in order to get to his job as a sales executive at a large company Insomnia has persisted despite treatment with cognitive behavioral therapy for insomnia (CBT-I), which includes both cognitive therapy and sleep hygiene education The patient is at risk for losing his job due to the effect of excessive sleepiness on his performance at work

13 Medical History No significant medical history The patient has had unsuccessful trials of numerous antidepressants including SSRIs, SNRIs, TCAs, mirtazapine, bupropion He was started on transdermal selegeline (12mg/24hr) 6 months ago and feels that his depressive symptoms are 90% improved

14 Pretest Question 2 Of the following choices, what would you do to improve this patient s insomnia? 1. Watchful waiting to see if insomnia improves with time 2. Reduce selegiline dose 3. Recommend removal of the selegiline patch before bedtime 4. Augment with an atypical antipsychotic 5. Augment with a benzodiazepine 6. Augment with trazodone 7. Augment with a non-benzodiazepine GABA A receptor modulator 8. Augment with ramelteon 9. Switch to a more sedating antidepressant

15 Attending Physician's Mental Notes 12-32% of patients taking transdermal selegiline experience insomnia (compared to 7% for placebo) and the risk of insomnia is dose-dependent Although selegiline-induced insomnia often resolves with time, this patient has been suffering for ~6 months and his insomnia is affecting his ability to function at work and home Given the patient s prior lack of response to numerous other antidepressant agents, switching from transdermal selegiline or lowering the dose may cause a loss of therapeutic gains There is some anecdotal information that removal of the selegiline patch prior to bedtime is helpful for some patients; however, this idea has never been clinically verified Trazodone is not recommended for use in patients taking an MAOI due to its serotonergic actions; however, trazodone can be used at low doses with caution by the expert

16 Attending Physician's Mental Notes (cont) Augmentation with an atypical antipsychotic that has sedating properties may be appropriate; however, there are cardiometabolic risks associated with atypical antipsychotc use Quetiapine does inhibit norepinephrine reuptake (increasing risk of blood pressure elevation) and act as an agonist at 5HT1A receptors (increasing risk of serotonergic toxicity). However, at low doses quetiapine binds primarily to histaminic H1 and adrenergic alpha1 receptors and acts as a hypnotic Given this patient s history of substance addiction, use of a benzodiazepine is not recommended first-line A non-benzodiazepine such as zolpidem, eszopiclone, or zaleplon may be safer for patients with a history of substance abuse The melotonergic M1/M2 receptor agonist ramelteon may also be a safe and effective choice for treating this patient s insomnia

17 Take-Home Points Insomnia is sometimes a symptom of depression that can be exacerbated by use of certain antidepressants, including MAOIs Given the consequences of excessive sleepiness on health and safety, it is essential that chronic, insomnia be addressed There are numerous options for treating insomnia in patients who are taking an MAOI

18 The Case: 39-year-old patient with a history of depression and alcohol abuse The Question: Is it bipolar disorder or unipolar depression? The Dilemma: Choosing among antidepressants, mood-stabilizers, and antipsychotics

19 Patient Intake 39-year-old female with major depressive disorder Began having problems with depressed mood as a teenager and began drinking shortly thereafter From ages 16-32, the patient suffered with a combination of alcohol abuse, alcohol dependence, and an untreated mood disorder Patient states that she was depressed ~60% of the time during these years She joined Alcoholics Anonymous and has been sober for the past 7 years She has also been treated with antidepressants during much of this time and reports being depressed ~30% of the time

20 Patient Intake (cont) The patient has no clear history of unequivocal hypomania; however, both amytriptyline and venlafaxine caused activation She has also responded recently to treatments that are more traditional for bipolar illness The patient reports crying spells due to sadness with a lack of desire, self-loathing, poor self-esteem, and poor energy Several weeks ago, the patient was suicidal and had a plan to jump off of the Golden Gate Bridge Her depressive symptoms have partially improved since starting aripiprazole 3 weeks ago

21 Medical History The patient has had numerous antidepressant trials including: Lithium Paroxetine Sertaline Fluoxetine Nefazodone Amitriptyline Venlafaxine Armodafinil augmentation Thyroid hormone augmentation

22 Current Medications Lamotrigine (100 mg twice per day) for headaches Escitalopram (20 mg/day) The patient has a difficult time tolerating more than this Bupropion 200 mg twice per day The patient relapsed when she discontinued escitalopram and bupropion in the past year Aripiprazole (10 mg/day) Lithium (450 mg/day)

23 Pretest Question 3 Of the following choices, what would you do? 1. Increase aripiprazole dose 2. Increase lithium dose 3. Switch to duloxetine 4. Switch to an MAOI 5. Try a non-pharmacological approach (ECT or TMS) 6. Augment with an atypical antipsychotic 7. Augment with a stimulant

24 Attending Physician's Mental Notes This patient has shown partial response to aripiprazole. Increasing the dose of arpiprazole up to 20 mg/day as tolerated may provide additional relief from depressive symptoms. However, aripiprazole may actually lose efficacy at higher doses Lithium may require a dose increase; however, lithium levels should be measured before increasing the dose Switching from bupropion to duloxetine (up to 120 mg/day) may be beneficial Given the treatment-resistant nature of this patient s depressive symptoms, a trial of an MAOI is warranted Augmentation with a non-pharmacological treatment such as ECT or TMS may also be helpful

25 Take-Home Points Partial response to antidepressant treatment is not good enough remission should be the goal In patients with partial response to antidepressant treatments, there are numerous options that can be explored

26 The Case: 82-year-old patient with major depressive disorder and tardive dyskinesia The Question: How should treatment be prioritized in the face of depression and a movement disorder? The Dilemma: How to treat one disorder without exacerbating another disorder?

27 Patient Intake 82-year-old woman with a long history of depression and anxiety She finally experienced relief on perphenazine/amitriptyline and took that for 6 years However, she began developing mouth movements and discontinued her perphenazine/amitriptyline 2 months ago She has spontaneous orobuccal facial dyskinesias that are both perioral and lingual; they also occur with swallowing Movement in her fingers, exacerbates the mouth movements She does not have muscle rigidity, blinking, obvious limb movements, or signs of parkinsonism in her gait Although she does walk with some hesitancy in her gait

28 Medical History Limited response to selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine, oral monoamine oxidase inhibitors (MAOIs) No improvement with electroconvulsive therapy (ECT) While on a regimen of venlafaxine plus lamotrigine plus topiramate, she suffered a fall attributable to the medications

29 Current Medications Enalapril for hypertension Meclizine for dizziness Benztropine for mouth movements Levothyroxine for augmentation of depression medication Temazepam for insomnia

30 Poll Question 1 Which concerns you most? 1. Her depressive relapse 2. Her tardive dyskinesia 3. Both are equally concerning

31 Pretest Question 4 In order to treat the patient's depression without exacerbating her tardive dyskinesia, one could prescribe an agent without dopamine-blocking or anticholinergic properties. Which of the following would you most likely recommend for this patient? 1. Selective serotonin reuptake inhibitor (SSRI) 2. Serotonin norepinephrine reuptake inhibitor (SNRI) 3. Noradrenergic and specific serotonergic antidepressant (mirtazapine) 4. Monoamine oxidase inhibitor (MAOI) 5. Tricyclic antidepressant with fewer anticholinergic properties (e.g., desipramine) 6. Lamotrigine 7. Lithium 8. Atypical antipsychotic 9. Non-medication intervention (ECT or TMS)

32 Attending Physician's Mental Notes Although she has not responded to oral MAOIs in the past, she has not yet tried transdermal selegiline, and it is possible that this would be an effective option for her Lithium has a narrow therapeutic index, and neurotoxicity may occur even at therapeutic doses in elderly patients When lithium is prescribed for elderly patients, they generally require lower doses and lower plasma levels (<0.6 meg/l) Blood levels would also have to be taken frequently because of possible interaction with enalapril

33 Attending Physician's Mental Notes (cont) An atypical antipsychotic, such as aripiprazole, quetiapine, or the olanzapine-fluoxetine combination may be effective for treating depressive symptoms Quetiapine in particular would not be expected to exacerbate tardive dyskinesia because it binds loosely to the D2 receptor and lacks powerful anticholinergic properties; however, it can cause sedation and thus might increase her risk of falling Although this patient did not respond to a previous trial of ECT, augmentation with a different nonpharmacological treatment such as TMS may be helpful

34 Pretest Question 5 How would you address this patient s tardive dyskinesia? 1. Watchful waiting for spontaneous recovery 2. Prescribe a dopamine-depleting agent 3. Prescribe amantadine 4. Prescribe a benzodiazepine 5. Prescribe a beta-blocker 6. Prescribe levetiracetam 7. Reinstitute the conventional antipsychotic 8. Discontinue beztropine 9. Discontinue meclizine

35 Attending Physician's Mental Notes Tardive dyskinesia will reverse in ~1/3 of patients over a 6-month period after the offending medication is discontinued Benztropine is a central anticholinergic medication; such agents can improve drug-induced parkinsonism but exacerbate or unmask tardive dyskinesia This effect may be reversible if the anticholinergic medication is discontinued. Thus, discontinuing benztropine could lead to improvement in her tardive dyskinesia Although it may not be feasible, one could also consider discontinuing meclizine, since this agent has many anticholinergic properties If tardive dyskinesia does not reverse, then management options include tetrabenazine, reserpine, amantadine, benzodiazepines, beta blockers, and levetiracetam, although none of these are particularly well studied Suppressive therapy by reinstituting the offending antipsychotic is a controversial option, but it may be appropriate for some patients, to mask tardive dyskinesia in the short-term

36 Take-Home Points Managing treatment-resistant depression is made even more difficult when comorbid conditions present The decision about which disorder to treat with priority may vary from patient to patient In this particular case, given the patient s age, the risk/benefit ratio is in favor of treating depression with priority However, her oral buccal dyskinesia will not be solely cosmetic if it leads to difficulty breathing or swallowing The evidence base to inform the management of patients with tardive dyskinesia is very limited; however, there are several options available