Valproate in the Treatment of Bipolar Disorder: Literature Review and Clinical Guidelines

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Lithium has unique pharmacokinetics because it is a monovalent cation. Arch Gen Psychiatry
1979;36902- 908 PubMed Google Scholar Crossref 50. Daley. Nimodipine monotherapy and
carbamazepine augmentation in patients with refractory recurrent affective illness. Addict Behav
2000;25307- 310 PubMed Google Scholar Crossref 57. Greenfield. Adjunctive lamotrigine as a
possible mania inducer in bipolar patients. Canadian Network for Mood and Anxiety Treatments
(CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of
CANMAT guidelines for the management of patients with bipolar disorder: update 2009. Arch Gen
Psychiatry 1991;4862- 68 Google Scholar Crossref 36. First. Clinical pharmacists can also provide
the patient with discharge counseling. Management of bipolar disorder during pregnancy and the
postpartum period. Lithium can cause a variety of benign and reversible cardiac effects, particularly
T-wave flattening or inversion (in up to 30% of patients), atrioventricular block, and bradycardia. 2,
22, 60 If a patient has significant preexisting cardiac disease, consultation with a cardiologist and an
electrocardiogram is recommended at baseline and during lithium therapy. J Clin Psychopharmacol
1992;1223S- 35S PubMed Google Scholar Crossref 29. McElroy. However, they still drank
significantly more than the valproate group, especially on measures of heavy drinking, and relapsed 1
month earlier to sustained heavy drinking. Patients taking these drugs should be regularly monitored
for weight, waist circumference, blood pressure, and serum glucose and lipid levels. 1
Extrapyramidal side effects are more common with first-generation antipsychotics, aripiprazole,
ziprasidone, and risperidone compared with olanzapine or quetiapine. 1 Refer to Table 1 for dosing
and side effects. J Clin Psychopharmacol 2000;201S- 17S PubMed Google Scholar Crossref 27.
Hammer. Primary alcohol use outcome included proportion of heavy drinking days (defined as ?4
drinks per day for women and ?5 drinks per day for men) and number of drinks per heavy drinking
day. Clinical trials for bipolar disorder and those for alcoholism systematically excluded serious co-
occurring conditions to reduce sources of variance. Stutzman Medicine, Psychology The mental
health clinician 2021 TLDR There is a lack of literature describing the long-term use of psychotropic
medications in youth—particularly with regard to neurobiological, physical, and social changes that
occur throughout development. Independence, Mo Independence Press1994; 51. Jennrich. The World
Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of
bipolar disorders: Update 2009 on the treatment of acute mania. Lithium can cause “floppy” infant
syndrome (e.g., low Apgar scores, lethargy, hypotonia, bradycardia, cyanosis, shallow respiration,
and poor sucking), hypothyroidism, and nontoxic goiters. Adjunctive group therapy through the
regular clinical program was allowed if requested by subjects, and sessions attended were recorded.
Economic and Social Research Council, National Institute for Health. The American Psychiatric
Publishing Textbook of Psychopharmacology. 4th ed. Washington, DC: American Psychiatric
Publishing; 2009:179. Carbamazepine is commonly used for both acute and maintenance therapy.
Arch Gen Psychiatry 1976;33766- 771 PubMed Google Scholar Crossref 44. Sobell. Lamotrigine in
the acute treatment of bipolar depression: Results of five double-blind, placebo controlled clinical
trials. Special issues in the treatment of pediatric bipolar disorder. Also known as Manic Depression
Results in pathological mood swings from mania to depression These mood swings occur
spontaneously. Am J Psychiatry 2003;1601263- 1271 PubMed Google Scholar Crossref. Serum
pregnancy tests were performed and the Revised Clinical Institute Withdrawal Assessment for
Alcohol Scale was administered when clinically indicated.
General treatment guidelines for the acute treatment of mood episodes in patients with bipolar I
disorder are found in Table 52-5. Am J Psychiatry 1992;1491633- 1644 PubMed Google Scholar 20.
Dilsaver. These include schizophrenia, schizoaffective disorder, posttraumatic stress disorder,
substance abuse (e.g., alcohol, cocaine, or amphetamines), and personality disorders. Addict Behav
2000;25307- 310 PubMed Google Scholar Crossref 57. Greenfield. Arch Gen Psychiatry
1999;56493- 502 PubMed Google Scholar Crossref 47. Perel. Adjunctive group therapy through the
regular clinical program was allowed if requested by subjects, and sessions attended were recorded.
The agent of choice depends on patient preference, tolerability, presentation and severity of
symptoms, and the drug’s side-effect profile. 20,21. It is less debilitating than bipolar I disorder, yet
it still has significant morbidity and mortality if left untreated. This disease is a mix between
schizophrenia and bipolar disorder. Additional alcohol use outcomes included proportion of any
drinking days, number of drinks per any drinking day, and time to relapse to sustained heavy
drinking (defined as 3 consecutive heavy drinking days). Our findings of slow improvement of
depressive symptoms suggest that bipolar alcoholic patients may be similar to nonalcoholic bipolar
patients in terms of time spent in a depressive state. 63. An observational study demonstrated a
reduction in suicide risk in patients on continued lithium treatment. Others: SSRIs, venlafaxine,
nefazodone, mirtazapine 3. Pharmacological interventions for acute bipolar mania: a systematic
review of randomized placebo-controlled trials. Serum levels should be drawn 10 to 12 hours after
the dose (trough levels) and at least 4 to 7 days after a dosage change. Social and familial factors in
the course of bipolar disorder: Basic processes and relevant interventions. Addict Behav 2000;25307-
310 PubMed Google Scholar Crossref 57. Greenfield. Major Depression. We all have experienced
the essential feelings associated with depression Feel down and listless Lack energy to do things.
Bipolar disorder in adults: pharmacotherapy for acute mania, mixed states, and hypomania.
UpToDate. Valproate is commonly used for this purpose but lacks regulatory approval and carries
appreciable risks. Defined by manic symptoms Elevated, expansive or irritable mood (or any
combination of these moods) plus (at least 3 or at least 4 if the mood is irritability). The American
Psychiatric Publishing Textbook of Psychopharmacology. 4th ed. Washington, DC: American
Psychiatric Publishing; 2009:697. However, this study does not address how and when lithium
should be initiated in patients who are currently suicidal. Antidepressants and psychostimulants in
pediatric populations: Is there an association with mania. Some data support the use of
oxcarbazepine, a 10-keto analogue of carbamazepine, in the treatment of bipolar disorder; however, it
is not approved for the treatment of bipolar disorder in the United States. Alcohol Clin Exp Res
2000;24666- 674 PubMed Google Scholar Crossref 56. Cornelius. Notably, no deleterious effects of
valproate on liver function enzymes occurred in this alcohol-dependent sample. Treatment plans
should be based on patient-specific characteristics, comorbid psychiatric and medical conditions, and
avoidance of drug interactions and adverse effects. 2 Specific Pharmacologic Therapies Lithium
Lithium was first used in 1949 as a treatment for mania and was approved in 1972 in the United
States for the treatment of acute mania and for maintenance therapy. Primary alcohol use outcome
included proportion of heavy drinking days (defined as ?4 drinks per day for women and ?5 drinks
per day for men) and number of drinks per heavy drinking day. We hypothesized that the valproate-
treated group would consume less alcohol, have a longer time to relapse to sustained alcohol use, and
achieve earlier remission from an acute bipolar episode than the placebo-treated group.
Patients who experience cycling should be managed with lithium, valproate, or lamotrigine. Br J
Addict 1988;83393- 402 PubMed Google Scholar Crossref 45. Weiss. We thank the individuals who
participated in the study, and we also thank Antoine Douaihy, MD, and the staff at the Center for
Psychiatric and Chemical Dependence Services of the Addiction Medicine Services, Western
Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center, Pittsburgh, for their
support. Maintenance lithium serum concentrations are usually measured every 3 months, but can be
adjusted to every 6 months for stabilized patients, and every 1 to 2 months for patients with
frequent mood episodes. 2 Lithium clearance rates increase by 50% to 100% during pregnancy and
return to normal postpartum; thus, lithium levels should be determined monthly during pregnancy
and weekly the month before delivery. Thrombocytopenia can occur at higher doses, and patients
should be monitored for bleeding and bruising. Rhew Medicine, Psychology Children 2022 TLDR It
is revealed that children with full-labeled psychiatric conditions are commonly administered drugs
that are not explicitly approved for either their disease state or age, including off-label and
unlicensed drugs. Menstrual cycle related mood changes in women with bipolar disorder. Bipolar
Disorder (BD)is an episodic, potentially life-long, disabling disorder Characterized by Mood
elevation Associated with significant Morbidity and Mortality if untreated Often underdiagnosed.
Clinical pharmacists can also provide the patient with discharge counseling. Moreover, inpatient
studies of mania have been compromised by attrition rates of up to 80% in placebo-treated arms by
the end of 3 weeks. 35 Lithium, a first-line medication for bipolar disorders, is the most acceptable
choice. If a patient demonstrates partial remission, clinicians may choose to augment therapy with
another drug to get the most benefit and then reevaluate the patient’s response. 1. Once diagnosed
with bipolar disorder, patients should remain on a mood stabilizer (e.g., lithium, valproate) for their
lifetime. The expert consensus guideline series: Medication treatment of bipolar disorder 2000.
Lithium can cause “floppy” infant syndrome (e.g., low Apgar scores, lethargy, hypotonia,
bradycardia, cyanosis, shallow respiration, and poor sucking), hypothyroidism, and nontoxic goiters.
There are case reports of possible lamotrigine-induced mania when added to lithium, carbamazepine,
and valproate. 79 In each of the cases reported, the patients had depressive mood symptoms or rapid
mood changes requiring additional therapy. 79. In men there may be increased incidence of mania
and substance use. 42. The only formulation approved in the United States for bipolar disorder is
extended-release carbamazepine, although other formulations can be used. Perphenazine was
permitted for treatment of psychotic symptoms. Benztropine mesylate was used to treat
extrapyramidal adverse effects. Practice guideline for the treatment of patients with bipolar disorder
(revision). Arch Gen Psychiatry 2003;60261- 269 PubMed Google Scholar Crossref 64. Bowden.
Polydipsia with polyuria and nocturia occurs in up to 70% of patients and can be managed by
changing to once-daily bedtime dosing. Higher serum concentrations of valproate were consistently
associated with decreased alcohol use outcomes. Potassium supplements have been suggested as
another treatment for lithium-induced polyuria. 22 Fluid restriction is not recommended because
dehydration increases the risk of lithium toxicity. The scope of this problem is more serious when
considering the broader concept of bipolar spectrum disorder, 4 and the high incidence of alcohol
and other SUDs among adolescent-onset bipolar disorders. 5. Nimodipine monotherapy and
carbamazepine augmentation in patients with refractory recurrent affective illness. First-line
medications include aripiprazole, carbamazepine, haloperidol, lithium, quetiapine, olanzapine,
risperidone, valproate or divalproex, and ziprasidone. Clinical trials for bipolar disorder and those for
alcoholism systematically excluded serious co-occurring conditions to reduce sources of variance.
Combination treatment can thus be considered, especially when patients show breakthrough mania
with the first agent. Lithium treatment and suicide risk in major affective disorders: Update and new
findings. Young Medicine, Psychology Journal of psychopharmacology 2016 TLDR The British
Association for Psychopharmacology guidelines specify the scope and targets of treatment for
bipolar disorder, and recommend strategies for the use of medicines in short-term treatment of
episodes, relapse prevention and stopping treatment.
Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomelitis.
Schizoaffective disorder is treated with mood stabilizers and antipsychotics as maintenance therapy.
Studies are warranted to replicate our current findings, determine whether those effects persist in
long-term treatment, and clarify valproate mechanism of action in reducing heavy drinking. For more
information, please refer to our Privacy Policy. Arch Gen Psychiatry 1991;4862- 68 Google Scholar
Crossref 36. First. See Table 52-2 for the evaluation and diagnostic criteria of mood episodes.
Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of
patients with bipolar disorder: consensus and controversies. This disease is a mix between
schizophrenia and bipolar disorder. Antidepressants and psychostimulants in pediatric populations: Is
there an association with mania. The Australian register of antiepileptic drugs in pregnancy: The first
1002 pregnancies. Clin Pharmacokinet 1977;273- 92 PubMed Google Scholar Crossref 49. Pandey.
Medication discontinuation occurs in up to 50% of patients secondary to intolerance of drug-induced
side effects. 50 Failure to recognize the disorder, reluctance to acknowledge it, or poor adherence
with treatment are reasons an estimated two thirds of patients with bipolar disorder do not receive
appropriate treatment. Nierenberg Medicine, Psychology Biological Psychiatry 2004 817 PDF Save.
1 2 3. Related Papers Showing 1 through 3 of 0 Related Papers Tables Ask This Paper 17 Citations
30 References Related Papers Table 1. If the antipsychotic is the patient’s maintenance therapy, the
dose should be increased or perhaps the medication should be changed altogether if the patient goes
into a manic episode. Suicidal ideation and suicide attempts in bipolar disorder type I: An update for
the clinician. Expand Save Long-term use of antidepressants, mood stabilizers, and antipsychotics in
pediatric patients with a focus on appropriate deprescribing D. Valproate use should be limited to
nonpregnant patients due to its tendency to cause neural tube defects in the fetus. 22,23. Moreover,
inpatient studies of mania have been compromised by attrition rates of up to 80% in placebo-treated
arms by the end of 3 weeks. 35 Lithium, a first-line medication for bipolar disorders, is the most
acceptable choice. Optimal serum maintenance levels may vary from patient to patient. 16,17 In
patients with renal impairment or thyroid disorder, serum lithium levels should be checked every 2 to
3 months in the first 6 months of treatment and every 6 to 12 months thereafter, or more frequently
if clinical status changes. Am J Psychiatry 1998;1551632 PubMed Google Scholar 62. Freeman.
Alcohol Clin Exp Res 1997;2186- 92 PubMed Google Scholar Crossref 23. Brady. Antidepressants
main induce a switch to mania (especially tricyclic antidepressants) 3. JAMA 1989;2621646- 1652
Google Scholar Crossref 19. McElroy. Bipolar disorder in adults: epidemiology and diagnosis.
UpToDate. Long-term adverse effects of lithium include nephropathy, hypothyroidism, goiter, and
possibly cardiac rhythm disturbances, especially in patients with pre-existing cardiac disease. 1,5. To
clinical pharmacists, obtaining an accurate and complete medication history is very important in
determining the appropriate therapy, or even identifying underlying medication-related causes of
disease cycling. Lithium levels are considered to be at steady state at approximately day 5, and serum
samples should be drawn 12 hours postdose. Serum levels should be drawn 10 to 12 hours after the
dose (trough levels) and at least 4 to 7 days after a dosage change. Lamotrigine: When and where
does it act in affective disorders. Arch Gen Psychiatry 2003;60261- 269 PubMed Google Scholar
Crossref 64. Bowden.