Mentoring Session: Participant...

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Mentoring Session:

Participant Cases

Handout for the Neuroscience Education Institute (NEI) online activity:


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


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”


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


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


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)


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



• 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


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


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


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)


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


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


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 GABAA receptor modulator

8. Augment with ramelteon

9. Switch to a more sedating antidepressant



• 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



(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


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


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


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


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


Medical History

• The patient has had numerous antidepressant trials including:

– Lithium

– Paroxetine

– Sertaline

– Fluoxetine

– Nefazodone

– Amitriptyline

– Venlafaxine

– Armodafinil augmentation

– Thyroid hormone augmentation


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)


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



• 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


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


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?


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


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


Current Medications

• Enalapril for hypertension

• Meclizine for dizziness

• Benztropine for mouth movements

• Levothyroxine for augmentation of depression

medication

• Temazepam for insomnia


Poll Question 1

Which concerns you most?

1. Her depressive relapse

2. Her tardive dyskinesia

3. Both are equally concerning


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)



• 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



(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 non-pharmacological treatment such as TMS may be helpful


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



• 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


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

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