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79-1
BIPOLAR DISORDER
Up All Night. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Level II
Jason M. Noel, PharmD, BCPP
The police bring a 28-year-old man to a mental health crisis center
after neighbors complain about his bizarre behavior and vocally
loud ranting. The patient has a previous history of psychiatric
admissions for acute mania. Although he has been prescribed lithium, his current serum concentration is subtherapeutic (0.1 mEq/L)
suggesting that he has not been adherent. After a physical examination and extensive interview, the patient is diagnosed with bipolar
disorder, current episode manic with psychotic features. In addition
to poor adherence to his psychotropic treatment, the stress of a
recent job loss and the use of a stimulant medication are proposed
to contribute to his recent decompensation. Pharmacotherapeutic
options for his current presentation include lithium (if nonadherence resulted in relapse), divalproex (also known as valproate), and
second generation antipsychotics. Other treatment options include
other atypical antipsychotics, carbamazepine, oxcarbazepine, or
topiramate. Adjunctive benzodiazepine therapy is advised to promote sleep and reduce agitation.
QUESTIONS
Problem Identification
1.a. List the manic symptoms present in this patient based on
DSM-5 diagnostic criteria for his bipolar disorder diagnosis.
• Abnormally elevated and expansive mood
• Grandiosity
• Decreased sleep
• Pressured speech
• Flight of ideas/racing thoughts
• Increased activity and agitation (psychomotor agitation)
• For ‘With Psychotic Features’ specifier: presence of delusions
(grandiose, hyper-religious, and paranoid)1
1.b. Identify possible triggers for this patient’s acute episode.
• Psychosocial stressor—loss of job
• Poor medication adherence
• Use of stimulant medication (modafinil)
• Episodic nature of illness
1.c. What data in this case can be used to assess the severity of
the current episode?
• Significant increase in activity
• Presence of psychotic symptoms
• Impairment in judgment
• Risk of harm to others (assaultive behavior)
1.d. Create a list of this patient’s drug therapy problems.
• Inadequately treated indication: bipolar disorder
• Drug-disease interaction: modafinil and bipolar disorder
• Possible adverse drug reactions: tardive dyskinesia from
haloperidol; psoriasis, GI upset, and diarrhea from lithium
Desired Outcome
2.List the subjective and objective parameters that can be used to
determine response to treatment.
• Subjective:
✓Normalization of mood
✓Reduction of agitated and impulsive behavior
✓ Reduction of thought disorder (delusions) and flight of ideas
✓Restoration of normal psychosocial function
• Objective:
✓Number of hours of sleep
✓Change in score in symptom rating scales (see self-study
assignment below)
Therapeutic Alternatives
3.a. What nondrug therapies might be useful for this patient?
• Ongoing psychotherapy to help the patient understand and
accept his diagnosis and improve treatment adherence.
• Educating the patient on possible precipitating factors for
relapse of bipolar symptoms (irregular or poor sleep, change in
employment or residence, and stimulant use) and the need for
long-term medication therapy.
• Instruction about the potential for refractory disease, including
loss of gray matter, due to repetitive nonadherence and relapse.
• Support and education about bipolar disorder for the patient’s
family, emphasizing the importance of minimizing family
stress. Poor family support is associated with increased risk of
relapse.
• Electroconvulsive therapy (ECT) is a useful intervention
typically reserved for cases of mania that has not responded
to other interventions or where usual pharmacotherapy is
contraindicated.
3.b.What feasible pharmacotherapeutic alternatives are available for treatment of bipolar disorder?
• Lithium is a reasonable choice if it can be shown that lithium
nonadherence resulted in relapse. It has been effective in treating prior episodes in this patient and is generally effective as
maintenance therapy to prevent manic and depressive episodes. It is also an inexpensive agent, and there is more than
50 years of clinical experience with this medication. However,
it may be less effective than other choices in mania with psychotic features. In addition, based on the information given, it
is unclear whether lithium nonadherence precipitated the present episode or whether nonadherence occurred after the onset
of mania (which would indicate lithium treatment failure).
The patient may be experiencing lithium-related adverse
effects such as GI upset, loose stools, psoriasis (which can be
secondary to or worsened by lithium), weight gain, and possible interference with thyroid function (thyroid-stimulating
hormone [TSH] is on the high end of the normal range). Other
disadvantages of using lithium include its slow onset of action
as monotherapy in acute mania, its narrow therapeutic index,
and the need for serum lithium concentration monitoring.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Bipolar Disorder
CASE SUMMARY
• Alcohol intoxication
CHAPTER 79
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• Subtherapeutic serum lithium level
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SECTION 7
Psychiatric Disorders
• Divalproex sodium may be more effective than lithium in mania
with psychotic features. The response to valproate is independent of previous lithium response. This drug is FDA approved
as a treatment for migraine headache prophylaxis, although it
is used at lower doses for that indication. The loading dose is
easy to calculate (20 mg/kg per day) and usually places patients
within the desired therapeutic range. Using a loading dose may
also provide more rapid onset of clinical effect.2 However, there
are no controlled studies of valproate for prophylaxis of mania
or depression, although open-label studies suggest benefit.
Adverse effects of valproate include GI side effects, transient
sedation, fine hand tremor, impaired platelet function (easy
bruising), thrombocytopenia, pancreatitis or hepatotoxicity
(rare), hair loss (2.6–12.0%), weight gain (common, 44%), and
abnormal thyroid function tests.
• Olanzapine (Zyprexa) is the first atypical antipsychotic to
have FDA approval for acute mixed or manic episodes of
bipolar I disorder and for maintenance treatment after achieving responder status. Olanzapine has demonstrated efficacy in
several studies when compared with placebo, valproate, and
lithium. Adverse effects include weight gain, hyperglycemia,
dry mouth, somnolence, postural hypotension, and dizziness.
• Quetiapine (Seroquel and Seroquel XR) is approved for bipolar
mania or mixed states as monotherapy or as adjunctive therapy
with lithium or divalproex. It is also approved for depressive
episodes in bipolar disorder. Quetiapine requires dose titration
to a target daily dose between 400 and 800 mg over the course
of 4–6 days. Dosages above 800 mg/day have not been studied
for bipolar disorder and have been linked to increased risk of
QTc prolongation. Dosing should be individualized based on
patient-specific response and tolerability.
• Lamotrigine (Lamictal) has been shown to be effective as
maintenance therapy for patients with bipolar I disorder. It is
approved by the FDA for the treatment of adults to delay the
time to recurrence of acute mood episodes (eg, depression and
mania) in patients treated with standard therapy. Additionally, lamotrigine significantly delayed time to intervention for
a depressive episode and showed limited efficacy in delaying
time to intervention for a manic/hypomanic episode, compared with placebo. The median dose of lamotrigine for treatment of bipolar maintenance in clinical trials was 200 mg/day.
Lamotrigine is started at 25 mg daily during the first 2 weeks
and then titrated slowly to reach 200 mg/day by 6 weeks after
the start of therapy. Dosages above 200 mg/day are not recommended. Alternative dosing is required for persons taking
valproate (beginning with 25 mg every other day to a maximum of 100 mg/day after 6 weeks). Higher doses are required
for persons taking carbamazepine (or other enzyme-inducing
drugs), beginning with 50 mg daily to a maximum of 400 mg
daily in divided doses after 6 weeks. Overall, lamotrigine is
well tolerated, with no apparent effects on weight, cognition,
or sexual functioning. The most common adverse events are
headache, nausea, infection, insomnia, somnolence, and rash.
In a review of lamotrigine-associated rash incidence in 12 multicenter trials (n = 3153), 11.6% developed a benign rash, with
<0.1% developing a serious rash.3
✓No formal recommendations exist for the duration of
lamotrigine maintenance therapy in bipolar disorder
although there are clinical trials demonstrating continued
efficacy as long as 18 months. Although not approved for
the short-term treatment of mood episodes, lamotrigine
has shown efficacy in the acute treatment of patients with
bipolar depression but has not demonstrated efficacy in the
treatment of acute mania.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
• Carbamazepine extended-release capsules (Equetro) is the only
carbamazepine formulation currently approved for bipolar
mania and mixed episodes. Other carbamazepine products are
not FDA-approved. The recommended initial dose is 400 mg
given in divided doses twice daily. The dose should be adjusted
in 200-mg increments to achieve optimal response. Doses
above 1600 mg/day have not been studied. It may be more
effective than lithium in treating mixed episodes. Efficacy
does not appear to be affected by previous nonresponse to
lithium. However, carbamazepine has been less well studied in
prophylaxis of bipolar disorder than lithium. Adverse effects
include rash (5–15%); photosensitivity; potential for severe
skin reactions (Stevens–Johnson syndrome); neurologic effects
(dizziness, sedation, fatigue, blurred vision, ataxia, and nystagmus); GI upset; and rare cases of agranulocytosis, syndrome
of inappropriate antidiuretic hormone secretion (SIADH), and
altered thyroid tests. Carbamazepine also has numerous drug
interactions with other hepatically metabolized drugs. Most
importantly, it is a CYP3A4 inducer and in fact initially induces
its own metabolism potentially requiring a dosage adjustment
after 1–2 weeks of treatment.
• Other atypical antipsychotics (eg, risperidone, paliperidone,
ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone,
cariprazine, and brexpiprazole) may be of value for short-term
use in patients with acute manic episodes associated with
bipolar disorder and can be used alone or in combination with
mood stabilizers such as lithium or divalproex. These agents
may be useful in controlling psychotic symptoms, agitation,
and aggressive behavior.
✓Some of the agents listed (eg, risperidone, aripiprazole,
cariprazine) are approved for short-term treatment of manic
or mixed episodes of bipolar disorder. In this setting, they
may be used as monotherapy or as a means to shorten
time to remission when used adjunctively with lithium or
divalproex.
✓Aripiprazole is also approved for maintenance therapy in
bipolar disorder.
✓Olanzapine/fluoxetine combination (Symbyax) and lurasidone are approved for bipolar depression. (Note: While
Symbyax is an option for some patients, it is not a reasonable
alternative for this patient at the present time. It may be used
if an underlying depressive episode is uncovered after the
current mania episode has been effectively controlled.)
• The following are available practice guidelines and treatment
algorithms for bipolar disorder:
✓ Texas Medication Algorithm Project (TMAP) Bipolar Disorder Algorithm4
✓Systematic Treatment Enhancement Program for Bipolar
Disorder (STEP-BD)5
✓Canadian Network for Mood and Anxiety Treatments
(CANMAT)6
✓National Institute for Health and Care Excellence (NICE)7
✓American Psychiatric Association8
Optimal Plan
4.a. What drug, dosage form, dose, schedule, and duration of
therapy are best for this patient?
• Given the acute and severe nature of this patient’s presentation,
a combination strategy with an anticonvulsant (divalproex or
carbamazepine) and atypical antipsychotic (eg, risperidone,
olanzapine, quetiapine, aripiprazole, asenapine, or cariprazine),
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• There is evidence (albeit controversial) that lithium is not as
effective as anticonvulsants (eg, divalproex, carbamazepine,
and lamotrigine) in mania with psychosis.
• We are not certain if this patient may have relapsed despite
ongoing lithium therapy or nonadherence.
• Starting the patient on an anticonvulsant (eg, divalproex, carbamazepine, lamotrigine) in addition to lithium with plans to
taper lithium after a positive response is achieved is also an
acceptable strategy.
• Restarting lithium alone may still be a good and viable treatment option. If the reason for the subtherapeutic level was
not due to intolerable side effects and if lithium is selected
and acceptable to the patient, the clinician should check prior
records to determine which dose resulted in serum concentrations of >0.8 mEq/L. The dose predicted by pharmacokinetic
equations ranges from 1500 to 2000 mg/day, whereas the
recommended starting dose from the prescribing information
is 900 mg/day. Because we know the patient’s previous dose
was 1,500 mg/day, if we are certain his therapeutic level was
achieved while he was actually taking that dose on a regular
basis, he should be restarted on this dose. Note: Patients who
are acutely manic may benefit from higher lithium levels initially to achieve more rapid symptom control. Therefore, dosing
at 1,800 mg/day initially with careful monitoring with dosage
reduction to 1,500 mg as the patient responds is also acceptable.
A lithium level should be obtained in 5 days, and the patient
should be monitored closely for signs and symptoms of toxicity.
• While not ideal for maintenance therapy, due to concerns about
tardive dyskinesia and metabolic effects, atypical antipsychotics may be used as monotherapy for the acute manic episode.
They may provide added short-term benefit, particularly for
the management of psychotic symptoms. Antipsychotics are
available in a range of dosage forms which allow for flexibility
in treating agitation or nonadherence. For example, liquid or
orally disintegrating tablets are options for patients with swallowing difficulties or who attempt to hide or “cheek” medications while on an inpatent unit. Antipsychotic options include:
✓Quetiapine is available as immediate- and extended-release
tablets. The extended release formulation allows for dosing
once daily, instead of twice daily. The dosage recommendation for day 1, 2, and 3 (and beyond) is 300, 600, and
between 400 and 800 mg, respectively. The low incidence
of extrapyramidal symptoms (EPS) with quetiapine is an
advantage of this product.
✓Aripiprazole is available as oral tablets, oral solution,
and orally disintegrating tablets. A depot injectable
✓ Asenapine is available only as sublingual tablets that dissolve
in the mouth. It is intended for absorption across the oral
mucosa. It is extensively metabolized by first-pass metabolism if swallowed. The recommendation is not to eat or drink
for 10 minutes after administration per labeling; however,
approximately 80% of the dose is absorbed in 2 minutes
and 90% in 5 minutes. It may be used for acute treatment
of mania and mixed states in bipolar disorder (10 mg BID
initial and target dose). Asenapine appears to have minimal
effect on weight or metabolic profile, prolactin, or blood
glucose, which makes it a good choice in this case. The side
effect of numbness of the tongue may be a concern for some
patients.
✓Risperidone is available as oral tablets, oral solution, and
a depot injectable (Risperdal Consta—primarily used for
psychotic disorders). It is another acceptable choice for use
alone or in combination with lithium or divalproex. The recommended initial dose is 2–3 mg/day titrated up to 6 mg/day
if needed. Risperidone has a higher incidence of extrapyramidal side effects than other atypical antipsychotics and may
also have a higher incidence of hyperprolactinemia.
✓Olanzapine—available as tablets, orally disintegrating tablets, and short-acting intramuscular injection. A long acting
injectable depot (Zyprexa Relprevv) is available for treatment of psychotic disorders. Olanzapine is typically given
on a once-daily schedule without regard to meals, starting at
10 or 15 mg once daily. Dosage adjustments should generally occur in 5-mg increments at intervals of not less than
24 hours. Short-term efficacy in acute mania has been demonstrated with a dosage range of 5–20 mg/day. The safety of
doses above 20 mg/day in mania has not been evaluated. For
agitation in bipolar mania (and schizophrenia) up to 10 mg
IM may be given every 2–4 hours (maximum of 3 doses per
24 hours).
• Carbamazepine extended-release capsule (Equetro) is the only
carbamazepine formulation currently approved for bipolar
mania and mixed episodes. Other carbamazepine products are
not FDA-approved. The recommended initial dose is 400 mg
given in divided doses twice daily. The dose should be adjusted
in 200-mg increments to achieve optimal response. Doses
above 1,600 mg/day have not been studied. Equetro and other
carbamazepine formulations have warnings regarding rash
(including Stevens–Johnson syndrome and toxic epidermal
necrosis). In addition, aplastic anemia and agranulocytosis are
a significant safety concern; thus, WBC and platelet counts
should be monitored closely. (Note: Carbamazepine can cause
fetal harm when administered during pregnancy. This is not
applicable in this patient, however.) Since carbamazepine is
known to be a CYP3A4 inducer, it can contribute to a significant number of drug–drug interactions.
• Oxcarbazepine, the 10-keto analog of carbamazepine is not
approved for bipolar disorder and only limited data exist on its
use in bipolar disorder. Its only advantage compared to carbamazepine is that it has somewhat milder adverse event profile.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Bipolar Disorder
• The use of divalproex allows for a rapid loading strategy, appropriate for acute mania. Divalproex sodium may be initiated
with a loading dose of 20 mg/kg per day (94 kg × 20 mg/kg =
1,880 mg).9 Based on available tablet strengths, a loading dose
of either 1,750 mg/day or 2,000 mg/day in 2–3 divided doses is
convenient and acceptable. Alternatively, valproate can be initiated at 250 mg TID with meals in accordance with prescribing
information. The dose of valproate should be titrated (generally
increased in increments of 250–500 mg) every 5–7 days until a
satisfactory response is seen. It is suggested that serum valproate
concentrations be maintained in the range of 50–100 mcg/mL
initially to increase the likelihood of achieving a response while
avoiding adverse reactions. Its effectiveness for mania with psychosis and as a prophylactic treatment for migraine headaches
make it a good choice for this patient.
(Abilify Maintena) is available for treatment of psychotic
disorders. It is approved for manic and mixed states in
bipolar disorder as monotherapy and adjunctive therapy
with lithium or valproate. It also has labeling for maintenance therapy in bipolar I disorder. The recommended
initial and target dose is 15 mg/day and can be titrated to
30 mg/day. It has a favorable profile for metabolic effects and
is association with mild treatment emergent EPS (primarily
akathisia).
CHAPTER 79
can be considered as initial treatment for the acute episode.
Factors that support this choice include the following:
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Psychiatric Disorders
Initial dose is usually 150–300 mg twice daily, with total daily
dose increased by 300–600 mg daily every 3–6 days up to
1,200 mg/day in divided doses. The American Psychiatric
Association treatment guidelines recommend oxcarbazepine
as an equivalent to carbamazepine9; however, TMAP Algorithm for Bipolar Disorder suggests carbamazepine in Stage 1b
(ie, alternative for the first step of therapeutic options) and
oxcarbazepine much lower, in Stage 3 (ie, third step of therapeutic options) where two-drug combinations are permitted,
following partial or nonresponse to trials of carbamazepine,
divalproex, lithium, and atypical antipsychotics.4
• Regardless of which regimen is selected for acute treatment,
a plan should be put in place for maintenance therapy to be
continued indefinitely (lifelong) based on the presence of the
following risk factors in this patient, which predict high probability of morbidity and recurrence:
✓The patient has experienced two prior episodes
✓Episodes of mania significantly limit this patient’s function
and quality of life
✓There is a family history of mood disorders
• Lamotrigine is approved for maintenance treatment of bipolar disorder to delay time to occurrence of mood episodes in
adults treated for acute mood episodes with standard therapy.
So in essence, it is adjunctive therapy which may be helpful in
the maintenance phase of treatment, which is not the scenario
for this patient. The longer titration requirements for lamotrigine also make it a less appropriate medication for this patient.
Lamotrigine is started at 25 mg daily during the first 2 weeks
and then titrated slowly to reach 200 mg/day by 6 weeks after
the start of therapy. Dosages above 200 mg/day are not recommended. Alternative dosing is required for persons taking valproate (beginning with 25 mg every other day to a maximum
of 100 mg/day after 6 weeks). Higher dosages are required for
persons taking carbamazepine (or other enzyme-inducing
drugs), beginning with 50 mg daily to a maximum of 400 mg
daily in divided doses after 6 weeks.
• Adjunctive use of a benzodiazepine is advised to promote sleep
and reduce agitation. If the patient has not discontinued his
haloperidol, this should be continued until symptoms have
remitted, at which time a slow taper can be instituted. If the
patient has discontinued his haloperidol and if it is advisable and acceptable to the patient to restart haloperidol, a
trial of benzodiazepine augmentation may be preferred. For
example, lorazepam, 1–2 mg PO/IM Q 2–8 H (maximum of
6 mg/24 hour) may be given initially, with titration based on
response. However, it is important to note that use of benzodiazepines in some patients may cause behavioral disinhibition
resulting in poor impulse control. The presence of psychotic
symptoms during the manic episode does not necessarily signal
the need for ongoing antipsychotic use after symptoms have
remitted. It should be noted that some atypical antipsychotics
have a maintenance therapy indication for bipolar disorder
patients. Benzodiazepines and antipsychotics can be tapered
and in some cases discontinued when the mania subsides.
Patients with affective disorder are at a higher risk for tardive
dyskinesia, even with atypical antipsychotics. This patient
already shows signs of tardive dyskinesia secondary to neuroleptic use (or possibly withdrawal dyskinesias if haloperidol
was recently discontinued).
• Adjunctive antidepressants may be an option; however, the
risks and benefits of their use should be very carefully considered. In addition, adjunctive antidepressants were no more
effective than placebo added to mood stabilizer therapy for
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
depressive episodes in bipolar disorder.10 Antidepressants may
also exacerbate manic symptoms in some patients.
4.b. What alternatives are appropriate if the initial therapy fails
or cannot be used?
• If two attempts at monotherapy with different agents are unsuccessful, combined use of two agents may be attempted (mood
stabilizer plus atypical antipsychotic, lithium plus carbamazepine, lithium plus valproate, or carbamazepine plus valproate).
Approximately 50% of patients respond to this strategy.
✓ See options in Question 4.a for “acceptable” choices if “good”
choices have failed or are not appropriate for clinical, historical, or other reasons (eg, previous history or family history
of drug misadventures or patient/clinician choice).
• Other alternative regimens include ECT, clozapine, topiramate,
or the calcium channel blocker, verapamil. These recommendations are primarily based on case reports or small studies,
few of which were done in refractory patients. Evidence for
the efficacy of verapamil is limited to acute mania responsive
to lithium.
Outcome Evaluation
5.What clinical and laboratory parameters are necessary to
evaluate response to therapy and to detect or prevent adverse
effects?
• Assess response through patient interviews and observation.
The first symptoms to respond are generally agitation, uncooperativeness, and decreased need for sleep. Assess speech (rate,
volume, degree of tangentiality, or flight of ideas), thought
content (preoccupation with sexual or religious themes, expansiveness, and delusions), appropriateness of appearance and
dress, and behavior on the inpatient unit. Rating scales such as
the Young Mania Rating Scale (YMRS), Montgomery-Asberg
Depression Rating Scale (MADRS), and Hamilton Depression
Rating Scale (HAM-D, HDRS) may also be used to assess treatment response.
• Monitor for adverse effects using a review of systems and
observation of the patient’s appearance. Parameters for individual drugs are included in the information below.
• Since most of the agents discussed in this case have a warning regarding suicidality, it is important to monitor closely for
suicidal behaviors and other signs that the patient may have
thought of suicide. Clinicians should be particularly vigilant
during initiation or changes in pharmacotherapy. Symptoms
related to energy, sleep, and appetite tend to improve faster
than mood-related symptoms such as helpless/hopelessness,
related to the depressive pole of bipolar disorder. As a result,
patients may now have the energy to act on their impulses,
increasing their risk for suicide attempts.
• Divalproex:
✓Monitor serum valproic acid concentrations weekly during dose titration. Thereafter, serum concentrations may
be monitored to assess adherence or to evaluate potential
toxicity. If the patient does not respond to therapy, the dose
may be increased to concentrations of 125–150 mcg/mL or
higher if tolerated.
✓ Approximately 50% of patients experience a 50% decrease in
symptoms within 3 weeks of starting therapy. Onset is generally within the first 2 weeks, with faster response seen when
loading doses are used (occasionally within 48 hours).
✓Laboratory monitoring should include liver function tests
(LFTs) and platelet counts at baseline and every 2 weeks
79-5
• Lithium:
✓Monitor serum lithium concentrations weekly for the first
month of therapy. Thereafter, monitoring is at the discretion of the clinician. Periodic monitoring may enhance
adherence.
✓The onset of response is generally within 1–2 weeks.
✓Obtain a pregnancy test in female patients before initiating
therapy.
• Atypical Antipsychotics:
✓Monitor blood glucose periodically due to the risk of hyperglycemia in persons with bipolar disorder.
✓Although weight gain liabilities vary among the drugs in
this class, educating regarding dietary intake should be done
along with routine weight evaluation.
✓A Dyskinesia Identification System: Condensed User Scale
(DISCUS) or Abnormal Involuntary Movement Scale
(AIMS) should be completed before starting the medication
and then quarterly for the assessment for tardive dyskinesia.
✓With the heightened concerns regarding both typical and
atypical antipsychotics’ various potential effects on QTc
interval prolongation, some clinicians advocate a baseline
and routine ECG while using these agents. However, there
is no requirement for ECG monitoring with any currently
marketed atypical agent.
• Carbamazepine or oxcarbazepine:
✓Carbamazepine concentrations are suggested weekly during
dose titration, then every 2 weeks for the first 6–8 weeks of
therapy. Thereafter, the routine monitoring of laboratory
values is unnecessary unless physical signs or symptoms of
adverse reactions develop. Limited data are available concerning serum concentration–response relationships. One
study indicates that levels of 6–10 mcg/mL may be more
likely to achieve efficacy; however, the Equetro manufacturer does not recommend therapeutic serum concentration
monitoring.
✓Approximately two-thirds of patients have an onset of effect
within 10 days.
✓Laboratory monitoring should include a CBC with differential, electrolytes, lipids, and LFTs every 2 weeks for the
first 6–8 weeks of therapy. Thereafter, routine monitoring
of laboratory values is often unnecessary unless interacting
medications are prescribed or discontinued or if physical
signs or symptoms of adverse reactions develop.
• Lamotrigine:
✓In two maintenance trials,11 lamotrigine monotherapy was
generally well tolerated, with common adverse events being
headache (19%), nausea (14%), infection (13%), and insomnia (10%). After 52 weeks of treatment, lamotrigine did not
appear to cause an increase in body weight.
Patient Education
6.What information should be provided to the patient to
enhance adherence, to ensure successful therapy, and to minimize adverse effects?
• General information:
✓ Patients and their families require ongoing education regarding bipolar illness and the need for long-term medications.
Referral to local community support groups such as the
National Alliance on Mental Illness (NAMI) or the Depression and Bipolar Support Alliance (DBSA) can help families
and consumers receive ongoing support.
✓Regarding medications, a single psychologist-directed therapy session when the patient is acutely ill is not satisfactory.
Most patients are not able to withstand long therapy sessions at this point in their illness, and it is not uncommon
for patients to be irritable, suspicious of your motives, or
uncooperative. Most patients with acute mania require hospitalization; therefore, the opportunity for ongoing therapy
should not be neglected.
✓ Patients must provide informed consent before starting therapy. In many cases, this is an opportune time to address any
concerns regarding medications (perform initial education)
and outline the proposed therapeutic plan. Patients may be
more likely to adhere to therapy if they are allowed to provide input into medication decisions and if they believe that
their opinions about therapy are important to the clinician.
If there is no compelling reason to use a specific medication,
it may be helpful to allow the patient to choose among the
two or three therapies of choice.
✓If the patient will not consent to therapy and is acutely agitated, most states provide avenues to medicate the patient on
an emergency basis (PRN) for a limited time; in some states,
a court order must be obtained to medicate the patient
against his or her will. Hiding the medication in food or
drink or surreptitiously administering medication is illegal,
is unethical, and does not foster a trusting relationship with
the patient.
✓After asking the patient what he already knows about
the prescribed medication, information can be presented
addressing missing information, including goals of therapy;
drug dosage; adverse reactions and how to minimize their
occurrence; and methods to deal with missed doses, acute
or concomitant medical illness, and drug interactions. Readers should fill in these data from their answers to the above
questions. Written information and a mechanism for the
patient to receive ongoing therapy after discharge are critical.
Information on lithium is given below as an example.
• Lithium carbonate film-coated tablets (eg, Lithobid):
✓Note: Lithium is used as the example here; if poor adherence
led to the patient’s deterioration, it should be attempted as
a retrial, unless the patient indicated intolerable adverse
events were the cause of nonadherence.
✓ This is a medication that you have taken before. It is intended
to help even out your mood swings; it may take 1 or 2 weeks
until you feel better.
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Bipolar Disorder
✓At baseline, monitor complete blood count (CBC) with
differential, serum creatinine and blood urea nitrogen
(BUN), electrolytes, urine-specific gravity, thyroid function
tests, and ECG. Laboratory monitoring should be repeated
1 month after stabilization on lithium, and then annually
(TSH may replace full thyroid function monitoring) or if the
patient becomes ill or adverse effects suggest monitoring is
warranted.
✓Approximately 0.1% of study participants receiving
lamotrigine developed a serious rash, including one case of
mild Stevens–Johnson syndrome. As a result, the dosage of
lamotrigine is titrated over a 6-week period to 200 mg/day
to minimize the incidence of serious rash.
CHAPTER 79
during dose titration. Thereafter, the routine monitoring
of laboratory values is unnecessary unless physical signs or
symptoms of adverse reactions develop.
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SECTION 7
✓Take this medication exactly as directed by your prescriber.
Do not take more of it, and do not take it more frequently
than your prescriber ordered.
✓It is important that you take the lithium every day, even if
you feel well.
✓Swallow the tablets whole; do not break, crush, or chew
them before swallowing.
Psychiatric Disorders
✓If you miss a dose, take it as soon as you remember; if it is
within approximately 6 hours of your next dose, skip the
missed dose and continue on your regular schedule.
✓This medicine sometimes causes dizziness or drowsiness;
make sure you know how you react to it before performing
any activities that require you to be fully alert.
✓Avoid altering the daily salt intake in your diet; this can
affect the lithium level in your blood.
✓ Drink adequate fluids (2–3 quarts/day) to maintain adequate
hydration; avoid prolonged exposure to the heat during the
summer months.
✓Avoid alcohol while taking this medication or limit your
alcohol intake to one or two drinks per day.
✓Do not take any over-the-counter or prescription medications without first consulting your prescriber.
✓It is important that you keep all follow-up appointments
with your prescriber.
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