Bipolar Depression Case

Tamara Bystrak
PharmD Candidate
8/16/2016
Providence PACE-RI

Discuss the presentation of bipolar disorder,
and possible treatment challenges in older
adults
Evaluate treatment options for bipolar
depression using the American Psychiatric
Association (APA) Practice Guidelines
Analyze the safety and efficacy of lamotrigine
add-on therapy based on the literature
Modify a psychiatric drug regimen to minimize
the risk of adverse effects

BG is a 60 year old woman with bipolar I
disorder. She has several active psychiatric
medications and reports good adherence.
However, BG still struggles with depressive
episodes. She survived a past suicide attempt
(hanging) which left her with neuropathy in
her legs. Several other comorbid disorders and
factors associated with aging impact clinical
decisions.

 “I felt happy for the first time in years after meeting my
grandchildren on vacation last week.” She hopes to stay
alive & well long enough to see them again next year.
 Patient voiced frustration over inability to lose weight
despite a healthy diet.
 She said she was also “nervous for my son to be in
France for the next month”, with all the attacks.
 Although she reported perfect adherence to
medication, she said she “hates that [she] has to take so
many pills”.

UNTREATED DISORDERS TREATED DISORDERS
• Urge incontinence
• Cataracts
• History of HTN
• Conversion disorder: hx
of MI, epilepsy, MS?
• Bipolar disorder, PTSD,
suicide attempt
• Abnormalities of gait and
mobility: foot drop
• Pain: polyosteoarthritis,
tendinitis, paresthesias
• Vertigo: history of falls
• COPD
• GERD
• Nicotine dependence: NRT
patches 7/31/15 – 3/21/16
• Vitamin D deficiency

Bipolar I: manic and depressive episodes
Bipolar II: hypomanic and depressive episodes
 Patients with untreated bipolar disorder often
experience over 10 episodes of mania and
depression during their lifetime
 Strains interpersonal relationships
 Common co-morbidities: substance use, anxiety,
insomnia, ADHD
 Adherence is often a concern
 10-15% suicide completion rates in Bipolar I
American Psychiatric Association. Practice Guidelines for the Treatment of Patients With Bipolar Disorder 2010. URL:
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf [accessed 2016 Aug 5].

Bipolar Symptoms homepage. A life guide to understanding the signs, symptoms, and treatment of manic depression.
Available at: http://bipolarsymptoms.com/symptoms-depression/. Accessed August 1, 2016.

 In patients over 65 years of age, bipolar disorder prevalence
is 0.1% - 0.4%
 5%–12% of geriatric psychiatry admissions are for bipolar
disorder
 Older patients with bipolar disorder may have longer
episodes or more frequent episodes of illness
 Older patients with bipolar disorder usually require lower
doses of medications
• Reduced renal clearance
• Reduced volume of distribution
• Increased risk of side effects

 English speaking
 Divorced, 3 children, lives alone
 HS graduate, fully literate
 Personal history of adult physical and sexual abuse
 Brother committed suicide, sister has depression
 Alcohol use: None
 Tobacco: 2-3 packs/wk in the past. Quit on 8/1/2016.
 Pathological gambling
 Enjoys PACE Bible study, trivia, shopping, walks,
music

Immunizations
• Up to date on Tdap, Pneumovax (PPSV23), yearly
influenza
• Eligible for Zostavax
Allergies
• Ciprofloxacin, E-mycin PCN, Penicillin, Shellfish –
swelling of face, eyes, tongue
• DEMEROL – GI upset
• Citrus intolerance

Brand Generic Dosing Indication
Vitamin D2 ergocalciferol
1 x 50000 UNT cap
monthly
Deficiency
Neurontin gabapentin 200mg twice a day Neuropathic pain
Eskalith
lithium
carbonate
300mg tab, 1 in AM
and 2 at night
Bipolar disorder
Prilosec omeprazole 20mg DR cap GERD
Risperidal risperidone
0.5mg tab twice a
day
Night terrors
Zoloft sertraline 200mg tab Depression, PTSD
Topamax topiramate
25mg tab in the AM
50mg tab at night
Mood stabilizer
Oleptro trazodone HCl 100mg at bedtime Depression
Flovent
fluticasone
44mcg
1 puff twice daily COPD

Brand Generic Dosing Indication Last Fill Date
Antivert meclizine hcl 12.5mg tab Vertigo 01/14/2016
Tylenol acetaminophen
325mg tab, take
1-2 every 8hrs
(max 3g)
Pain
06/01/2016
Ventolin albuterol
1 puff every 4-6hr
as needed
COPD
07/15/2016

BP: 122/70 mmHg
HR: 70bpm
RR: 18 breaths/min
Ht: 64” Wt: 164lb BMI: 28
Cockgroft Gault CrCl = 64mL/min using AdjIBW
Lithium: 0.8 MEQ/L consistently (0.5-1.3)
Chem-7, CBC, lipids, LFTs WNL

GDS: 9/15 (1/20/2016)
• 15 Y/N Questions
• 0-5 = Normal
• 6-9 = Mild depression
• 10-15 = Severe depression
 Patient still reports episodes of depression,
indicating bipolar disorder may entirely managed
 Patient did not report any recent episodes of mania
in the last 6 months

 Falls Risk - Risperidone, sertraline, trazodone, lithium, topiramate
 Beers List – Risperidone
• Increased risk of stroke and mortality in persons with dementia
• May cause SIADH or hyponatremia
• May cause ataxia, impaired psychomotor function, syncope
 Drug-Drug Interactions
• Lithium & trazodone &sertraline – serotonin syndrome risk
• Lithium & Risperidone - may result in weakness, dyskinesias,
extrapyramidal symptoms, encephalopathy, or brain damage.
DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/
(accessed 8/05/2016.
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American geriatrics society 2015 updated beers criteria for
potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11) 2227-46.

 First line: Lithium [I] or Lamotrigine [II]
 Optimize the dose of the maintenance medication
(check serum level) before adding a new agent
 Simultaneous treatment with lithium and an
antidepressant in more severe cases [III]
 Interpersonal therapy and cognitive behavior
therapy (CBT) may be useful when added to
pharmacotherapy [II]

 When first-line medication at the optimal dose
fails, add lamotrigine [I], bupropion [II], or
paroxetine [II].
 Alternative: add another selective serotonin
reuptake inhibitor [SSRI] or venlafaxine [II] or a
monoamine oxidase inhibitor (MAOI) [II].
 While MAOIs have generally demonstrated good
efficacy, their side effect profile is a limitation

 Antidepressants have shown good efficacy in
the treatment of unipolar depression
 However, antidepressant monotherapy is not
recommended in bipolar disorder, given the risk
of precipitating a switch into mania.
 Tricyclic antidepressants (TCA) may carry a
greater risk of precipitating a switch into mania

 Following remission of an acute episode, patients may
remain at high risk of relapse for up to 6 months
 The medications with the best evidence to support their use
in maintenance treatment include
• Lithium [I] and valproate [I]
• Alternatives: lamotrigine [II] or carbamazepine or
oxcarbazepine [II]
• If a medication was used to achieve remission from a
recent depressive or manic episode, it should be
continued [I].

 For patients treated with an antipsychotic during an acute episode,
the need for ongoing antipsychotic treatment should be reassessed
before kept on as maintenance
 Antipsychotics should be discontinued unless required for control of
persistent psychosis [I] or prophylaxis against recurrence [III].
 There is no definitive evidence that antipsychotic efficacy in
maintenance treatment is comparable to that of agents such as
lithium or valproate.

 Older patients may be more likely to develop
cognitive impairment with medications such as lithium or
benzodiazepines
 They may also have difficulty tolerating antipsychotic medications
and are more likely to develop extrapyramidal side effects (EPS) and
tardive dyskinesia than younger individuals
 With some antipsychotics and antidepressants,
orthostatic hypotension may be particularly problematic and
increases the risk of falls.
 Use of benzodiazepines and of neuroleptics also has been
associated with greater risks of falls and hip fractures in geriatric
patients

 FDA approved treatment for bipolar disorder and seizures, due
to it’s actions blocking voltage gated sodium channels
 More effective on depressive bipolar symptoms (depressive
cognition, psychomotor slowing) vs. manic bipolar symptoms
 Available as a immediate-release tablet, chewable tablet, orally
disintegrating tablet, and extended-release tablet
US Food and Drug Administration (FDA). Lamictal: Labeling History Table.
URL:http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM234474.pdf [accessed 2016 Aug 8]

Diplopia (25%)
Skin rash (7-14%)
Drowsiness, fatigue (8%)
GI: N/V, abdominal pain (5-9%)
Gait abnormality: ataxia, tremor (7%)
Fever (1-15%)
Dizziness, anxiety, insomnia (5%)
Risk of new or worsening depression
Gold Standard, Inc. Lamotrigine Adverse Eventss. Clinical Pharmacology [database online]. Available at:
http://www.clinicalpharmacology.com.uri.idm.oclc.org Accessed: Aug 05, 2016.

Most common reason for discontinuation
Usually occurring in first 2-8wks
Varying in severity: erythema multiforme, Stevens-
Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
< 0.1%
Received a Black Box Warning in 1997 for “serious, life-
threatening, and fatal rashes”
In clinical trials of mood disorder, rate of serious rash was
0.08% in adults receiving Lamictal as initial monotherapy,
and 0.13% in adults receiving Lamictal adjunctively
Low starting doses and slow escalating minimizes risk
URL:http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM234474.pdf [accessed 2016 Aug 8]

FOAMcast. A Free Open Access Emergency Medicine-Core Content Mash Up. Available at: http://foamcast.org/2015/03/01/episode-25-skin-and-
skin-structure-infections/ [accessed 2016 Aug 08].

 “Efficacy and safety of lamotrigine as add-on to lithium in
bipolar depression”. A multicenter, double-blind, placebo-
controlled trial (2009)
 N=124 patients with bipolar I or II and major depressive
episodes, taking baseline lithium (0.6-1.2 mmol/L)
 Intervention: lamotrigine titrated to 200mg daily or placebo
 Primary Endpoint: Depression measured using
Montgomery-Asberg Depression Rating Scale (MADRS) score
after 8 weeks of treatment
van der Loos ML, Mulder PG, Hartong EG, Blom MB, Vergouwen AC, de Keyzer HJ, Notten PJ, Luteijn ML, Timmermans MA, Vieta E, Nolen WA; LamLit Study
Group. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin
Psychiatry. 2009 Feb;70(2):223-31.

Results
1) Significant reduction in scores on MADRS (-15.38 vs.
-11.03) p=0.024
2) Significantly more patients had a response to
lamotrigine than placebo (52% vs. 32%) defined as
at least 50% on the MADRS
3) Switch to mania occurred in 7.8% on lamotrigine
and 3.3% on placebo
van der Loos ML, Mulder PG, Hartong EG, Blom MB, Vergouwen AC, de Keyzer HJ, Notten PJ, Luteijn ML, Timmermans MA, Vieta E, Nolen WA; LamLit Study
Group. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin
Psychiatry. 2009 Feb;70(2):223-31.

 N=124 patients with bipolar I or II and major depressive episodes
randomized to lamotrigine 200mg or placebo
 Nonresponders at 8 wk received paroxetine add-on for another 8
weeks
 Patients followed for 68 weeks or until relapse/recurrence
Results
• Addition of paroxetine in nonresponders lead to further
improvement with no significant difference between groups at
wk 16
• Time to relapse/recurrence was significantly longer in the
lamotrigine group (10 months) vs. placebo (3.5 months)
van der Loos ML, Mulder P, Hartong EG, Blom MB, Vergouwen AC, van Noorden MS, Timmermans MA, Vieta E, Nolen WA; LamLit Study Group. Long-term outcome
of bipolar depressed patients receiving lamotrigine as add-on to lithium with the possibility of the addition of paroxetine in nonresponders: a randomized, placebo-
controlled trial with a novel design. Bipolar Disord. 2011;13(1):111-7.

 Multisite, open-label, 12 week prospective trial
 N = 57 older adults (age 60+) with bipolar disorder
 Baseline: Patients were receiving no treatment, or treatment at
steady doses for 30 days before
 Intervention: lamotrigine 25mg daily titrated to goal
• 200mg daily
• 100mg daily if concurrent valproate
• 400mg daily if concurrent carbamazepine
• Maximum dose before intolerable side effects
 Primary Endpoint: Change in MADRS from baseline
Sajatovic M, Gildengers A, Al Jurdi RK, Gyulai L, Cassidy KA, Greenberg RL,et al. Multisite, open-label, prospectivetrial of lamotrigine for geriatric bipolar
depression: a preliminary report.Bipolar Disord. 2011;13(3):294-302

Results:
1. There was significant improvement in the MADRS, HAM-D, CGI-BP, and
in most domains on the WHO-DAS II
 31 (57.4%) met remission criteria (final MADRS score < 10)
 35 (64.8%) met response criteria. (50% or greater reduction in
MADRS score from baseline)
2. 19/57 (33.3%) dropped out prematurely
 6 due to adverse events: 4 rash, 1 manic switch, 1 hyponatremia
3. Most common AE:
 Insomnia (25%), weight loss (21%), increased dream activity (21%),
polyuria/polydipsia (19%), weight gain (16%), reduced libido (16%),
increased sleep (16%), fatigue (14%) unsteady gait (14%)

Geriatric Bipolar
Depression Trial
Cont.

Minimizing maintenance regimen:
Lithium (mood stabilizer) – Keep
Risperidone (antipsychotic) - Discontinue
Sertraline (antidepressant) - Discontinue
Trazodone (antidepressant) - Keep
Topiramate (mood stabilizer) - Discontinue

 Lithium: first line for maintenance and is the only agent
that shows efficacy against suicidal ideation
 Risperidone: high risk of falls, metabolic AE, EPS, SIADH,
and and minimal if any benefit over mood stabilizers
alone in mania
 Sertraline and Trazodone: therapeutic duplicates, as both
are serotonergic antidepressants. Together they increase
risk of serotonin syndrome. Either can be discontinued
 Topiramate: was added to balance the Risperidone and
antidepressant effects, which would no longer be
necessary

 Typically reduce dose by 10-20% every 1-2 weeks to avoid AE
 Withdrawal symptoms may include: N/V, mood lability, insomnia,
anxiety, muscle pain, HA, fatigue
Plan
1. Taper off sertraline and risperidone together
2. Sertraline: 200mg, 175mg, 150mg…25mg, 12.5mg, stop
3. Risperidone: 1mg, 0.75mg, 0,5mg, 0.25mg, 0.125mg, stop
4. Can increase dose of trazodone by 25mg daily each week, to a
max 400mg daily to compensates for any rebound depression
5. Taper off topiramate once stable one month without sertraline
and risperidone
6. Topiramate: 75mg, 50mg, 25mg, 12.5mg, stop
7. Patient remains on lithium and trazodone alone
Thinking About Mental Health. Myths, treatment risk & alternatives. Available at: http://www.mythsandrisks.info/coming-off-psych-drugs.html .
Accessed Aug 10, 2016.

• If residual depressive symptoms occur, lamotrigine is the
preferred add-on to therapy with lithium. Start low at
follow careful titration with monitoring for rash.
• If serious lamotrigine rash occurs, discontinue. May
increase trazodone dose to 400mg max or replace with
another antidepressant (bupropion or paroxetine
preferred). SNRI’s or bupropion could give dual benefit
• If manic symptoms occur, evaluate for antidepressant
mediated switching. An atypical antipsychotic (lurasidone,
aripiprazole best based on side effects) may be added
acutely. Do not continue long term use of antipsychotic
unless severe psychosis persists

URL:http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM234474.pdf [accessed 2016
Aug 8]

 The APA guidelines can be used to help create comprehensive
treatment plans for older adults with bipolar disorder.
 Using multiple psychotropic drugs to treat bipolar disorder
often poses greater risk than benefit in geriatric populations.
 There is sufficient evidence to support the safety and efficacy of
lamotrigine in bipolar depression.
 Lamotrigine should be initiated at a low dose and titrated up
slowly, with close monitoring for rash and rebound mania.

• Bipolar Symptoms homepage. A life guide to understanding the signs, symptoms, and
treatment of manic depression. Available at: http://bipolarsymptoms.com/symptoms-
depression/. Accessed August 1, 2016..
• American Psychiatric Association. Practice Guidelines for the Treatment of Patients With
Bipolar Disorder 2010. URL:
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pd
f [accessed 2016 Aug 5].
• DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village,
Colorado, USA. Available at: http://www.micromedexsolutions.com/ (accessed 8/05/2016.
• American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American geriatrics
society 2015 updated beers criteria for potentially inappropriate medication use in older
adults. J Am Geriatr Soc. 2015;63(11) 2227-46.
• US Food and Drug Administration (FDA). Lamictal: Labeling History Table.
URL:http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterial
s/PediatricAdvisoryCommittee/UCM234474.pdf [accessed 2016 Aug 8]
• Gold Standard, Inc. Lamotrigine Adverse Eventss. Clinical Pharmacology [database online].
Available at: http://www.clinicalpharmacology.com.uri.idm.oclc.org Accessed: Aug 05, 2016.

• FOAMcast. A Free Open Access Emergency Medicine-Core Content Mash Up.
Available at: http://foamcast.org/2015/03/01/episode-25-skin-and-skin-structure-
infections/ [accessed 2016 Aug 08].
• van der Loos ML, Mulder PG, Hartong EG, Blom MB, Vergouwen AC, de Keyzer HJ,
Notten PJ, Luteijn ML, Timmermans MA, Vieta E, Nolen WA; LamLit Study Group.
Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar
depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry.
2009;70(2):223-31.
• van der Loos ML, Mulder P, Hartong EG, Blom MB, Vergouwen AC, van Noorden
MS, Timmermans MA, Vieta E, Nolen WA; LamLit Study Group. Long-term outcome
of bipolar depressed patients receiving lamotrigine as add-on to lithium with the
possibility of the addition of paroxetine in nonresponders: a randomized, placebo-
controlled trial with a novel design. Bipolar Disord. 2011;13(1):111-7.
• Sajatovic M, Gildengers A, Al Jurdi RK, Gyulai L, Cassidy KA, Greenberg RL,et al.
Multisite, open-label, prospectivetrial of lamotrigine for geriatric bipolar
• Thinking About Mental Health. Myths, treatment risk & alternatives. Available at:
http://www.mythsandrisks.info/coming-off-psych-drugs.html . Accessed Aug 10,
2016.

Bipolar Depression Case

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