What Are the Best Medication for Bipolar Depression Reviews
Published November sixteen, 2011
Bipolar II Disorder in Adults: A Review of Direction Options
Soheyla Mahdavian, PharmD
Assistant Professor for Chemist's shop Practice
Florida A&M University Higher of Pharmacy and Pharmaceutical Sciences
Tallahassee, Florida
Marlon Honeywell, PharmD
Interim Associate Dean for Academic Affairs and Professor
Florida A&M University College of Pharmacy and Pharmaceutical Sciences
Tallahassee, Florida
Tiffany Welch, PA
Bond Community Wellness Center
Tallahassee, Florida
US Pharm. 2011;36(11):HS17-HS24.
Bipolar disorder is characterized by pathologic variations in mood, with periods of mania, hypomania, psychosis, and depression. The two most common types, bipolar I and bipolar 2, differ in the presentation of mood variations. The grade of bipolar Ii is less well studied and less understood than bipolar I disorder. Patients with bipolar I disorder take episodes of total mania alternating with episodes of major depression,ane,2 whereas patients with bipolar II disorder pre-sent with ane or more episodes of major depression with at least one hypomanic episode.1 Bipolar Two can too manifest itself as a mixed country, which is the presence of both depressive and mood elevated symptoms simultaneously.3 Patients with bipolar II disorder display fewer manic symptoms than those with bipolar I disorder; both weather condition may have an equivalent touch on on quality of life and may also be associated with increased suicide risk.3 Patients may also present with rapid-cycling bipolar disorder, which consists of at least iv discrete episodes of mania or depression in a single year, demarcated by clear periods of remission or by switches to episodes of opposite polarity.four
The criteria for mania and hypomania are outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-4-TR).4
Bipolar 2 disorder shares some similarities with bipolar I disorder (Effigy one). Approximately threescore% to 70% of the hypomanic episodes that occur in patients with bipolar Two disorder occur immediately before or after a major depressive episode, with feature patterns that are unique to each individual.4 Equally with bipolar I disorder, the interval between episodes seems to decrease with age, though approximately five% to xv% of patients experience rapid cycling.iv The more episodes a patient experiences, the poorer the prognosis. Fortunately, the majority of patients return to a normal functional level between episodes, nevertheless 15% of patients go along to experience mood lability between episodes.4 Some evidence has shown that sleep-wake wheel disturbances can precipitate or exacerbate a hypomanic or depressive episode. If a patient experiences a manic episode, an episode of psychosis, or a mixed episode, the diagnosis changes to bipolar I disorder.
Epidemiology
The prevalence of bipolar 2 disorder (ane.1%) is slightly higher than the prevalence of bipolar I disorder (1%) in adults in the Usa.iii,5 The true prevalence of bipolar disorder is uncertain considering the diagnosis is likely to be missed, peculiarly when patients are seen with depression and not specifically questioned almost symptoms that may suggest prior episodes of mania or hypomania.3 Bipolar Two disorder is more than common in women, whereas bipolar I affects men and women equally.3 The age of onset of bipolar II is generally betwixt 15 and thirty years of historic period, with less common new diagnoses made in babyhood and in adults over the age of 65 years.3
Pathophysiology
The search for genetic candidates has been the subject of considerable study, although no single gene has been identified.3 Some studies suggest a role for the tryptophan hydroxylase 2 (TPH2) gene, which is an enzyme in the constructed pathway for serotonin.iii In addition, genomic studies accept suggested an association with the CACNA1C gene, which codes for a subunit of calcium channels. This gene is involved in aqueduct gating, supporting the use of lithium, which in turn results in the down-regulation of calcium channel subunits.3 In that location have besides been studies that have revealed abnormalities of the corpus callosum, amygdala, dopamine D4 receptor genotype, and dopamine transporter cistron SLC6A3, and decreased protein kinase in platelets.5
Other central nervous arrangement (CNS) neurotransmitters involved in action modification include serotonin, dopamine, norepinephrine, acetylcholine, gamma-aminobutyric acid (GABA), and glutamate.6 The footing for almost pharmacotherapy is aimed at regulating these neurotransmitters to restore normal mood and knowledge.5 Other nonpharmacologic ways to regulate these neurotransmitters may include meditation, deep relaxation, and do, which increase endogenous opioid and nicotinic receptor function.5
Evaluation and Assessment
Many psychiatric weather condition may mimic and sometimes coexist with bipolar 2 disorder. These include schizophrenia, schizoaffective disorder, posttraumatic stress disorder, substance abuse (e.yard., alcohol, cocaine, or amphetamines), and personality disorders. Manic episodes can too occur in some medical conditions, such as thyrotoxicosis, partial circuitous seizures, systemic lupus erythematosus, cerebrovascular accidents, HIV infection, third syphilis, and other CNS insults (i.due east., steroid-induced mood symptoms or encephalopathy).3 For these reasons, it is prudent to carefully assess and evaluate patients holistically who nowadays with these variations in mood. Physical examination, with detail focus on neurologic and endocrine systems, signs of substance abuse, symptoms of trauma to the CNS, and laboratory testing (including thyroid testing, CBC, blood chemistries, and urine toxicology testing), should be conducted to rule out other etiologies of mood disorders.3
Conducting a mental condition test (MSE) is also an essential component of evaluating mental health. The MSE is used to assess the patient'due south general appearance and demeanor, speech, motility, and interpersonal relatedness with the examiner and others.five The MSE addresses: i) mood and cognitive abilities; 2) issues of safety, by exploring suicidal or homicidal ideation; iii) subtle forms of psychosis, such as paranoia or delusional states; 4) overt psychosis; and 5) the patient's insight and judgment, which is integrated into the evaluation of the global mental land of the patient at that moment. Though a limitation of this examination is its subjectivity, it is essential in the diagnosis and management of bipolar 2 disorder.5
Treatment and Management
Prior to beginning treatment, patients should be clinically assessed for their rubber and presenting symptoms. Patients who present with acute manic episodes should be assessed for their chance of suicide, aggressiveness, and potential for violence to others.1 Antidepressants, nicotine, and alcohol should be discontinued, and any substance abuse problems addressed. Other psychosocial problems should be evaluated in the patient.
Handling of elevated mood syndromes is based upon what has been established for bipolar I disorder, even though bipolar Two disorder is more than prevalent. Most published studies take focused upon bipolar I patients with mania, and few studies have focused on the treatment of hypomania.1
Mania and Hypomania
The goal of treatment is full remission of the elevated mood syndrome, with caution not to have unrealistic goals set for the patient.i Drug classes commonly used to induce remission in patients with acute mania, mixed states, or moderate-to-severe hypomania include lithium, anticonvulsants, antipsychotics, and benzodiazepines (TABLE ane).one Most treatment modalities are afforded 2 weeks to decide efficacy; studies show that if a patient does not remit within 2 weeks, an culling agent may be used. If a patient demonstrates fractional remission, clinicians may cull to broaden therapy with another drug to get the most benefit and then reevaluate the patient's response.1
Many drugs are effective every bit monotherapy for treating acute mania, mixed states, and moderate-to-severe hypomania. Offset-line medications include aripiprazole, carbamazepine, haloperidol, lithium, quetiapine, olanzapine, risperidone, valproate or divalproex, and ziprasidone. Several meta-analyses have shown that the aforementioned drugs used as monotherapy may allow for pregnant improvement on the mania rating scale and response compared with placebo, and take also shown like efficacy beyond these first-line medications.i,7-9
Depression
For bipolar depression, all antidepressants should be discontinued; monotherapy with an antidepressant is not recommended in social club to prevent precipitation of manic or hypomanic episodes.1,10 The likelihood of this switch to hypomania, withal, is less in patients with bipolar II disorder as compared with those with bipolar I. The kickoff-line pharmacologic treatment for bipolar depression is either lithium or lamotrigine, or, as an alternative for more severely ill patients, lithium can be given with an antidepressant.10 If patients on treatment suffer a breakthrough depressive episode, the dose of the therapy should be optimized before adding other agents. If dosing optimization is not sufficient, lamotrigine, bupropion, or paroxetine may be added.10 Alternative treatment modalities may include other selective serotonin reuptake inhibitors (SSRIs), venlafaxine, or a monoamine oxidase inhibitor (MAOI).
Rapid Cycling
If the patient experiences rapid cycling, the individual should be evaluated for underlying conditions, such as alcohol abuse or hypothyroidism, which may contribute to cycling.10 Certain medications, specially antidepressants, may also precipitate cycling and should be tapered downward. Patients who feel cycling should be managed with lithium, valproate, or lamotrigine.
Pharmacologic Therapy
Lithium
Lithium has been around for several decades and is approved by the FDA for handling of mania and for treatment and prophylaxis of bipolar disorder. At that place accept been more than controlled trials demonstrating the efficacy of lithium monotherapy for the treatment of astute mania (including patients with psychosis) than for any other medication.11 Lithium has likewise shown efficacy for bipolar depression and preventing suicidality.12,xiii
Lithium causes a number of biochemical and biological effects, although the exact mechanism for mood stabilization remains unknown.xiii A review of 32 trials shows that lithium is the only mood stabilizer that has lowered the suicide rate in patients with bipolar disorder.xiv Lithium has likewise been shown to mitigate relapse of bipolar disorder from 61% to 40%, and it prevents more manic episodes when compared with depressive episodes.15
Dosing and Monitoring: The starting dose of lithium is usually 300 mg ii to three times daily (start with smaller doses in the elderly, e.thousand., 150 mg twice daily), which should be increased past 300 to 600 mg every 1 to 5 days based upon response, tolerability, and body mass index.1 The target dose is unremarkably 900 to 1,800 mg daily in divided doses. Lithium has a narrow therapeutic index (0.8-1.2 meq/Fifty); serum lithium levels should be checked at a minimum of every half dozen months in stable patients, or more oftentimes if clinical condition changes. Lithium levels should be checked 5 days subsequently dosages are adapted—in one case the drug reaches steady state concentration. Optimal serum maintenance levels may vary from patient to patient.xvi,17 In patients with renal impairment or thyroid disorder, serum lithium levels should exist checked every two to 3 months in the first 6 months of handling and every half dozen to 12 months thereafter, or more oft if clinical status changes.
Side Furnishings: The most mutual astute side effects include nausea, tremor, polyuria and thirst, weight gain, loose stools, and cognitive impairment.12,eighteen,xix Whatsoever exacerbation of these side furnishings may signal lithium toxicity and should be addressed. Long-term agin effects of lithium include nephropathy, hypothyroidism, goiter, and perchance cardiac rhythm disturbances, specially in patients with pre-existing cardiac disease.1,five
Anticonvulsants
Anticonvulsants are used in the handling of bipolar Ii disorder considering they: 1) decrease encephalon excitation; 2) enhance inhibition by blocking low-voltage sodium-gated channels; iii) lower glutamate and other excitatory amino acids; and 4) potentiate the levels of GABA. Anticonvulsants that are used in bipolar disorder include valproate or divalproex, lamotrigine, and carbamazepine. The amanuensis of selection depends on patient preference, tolerability, presentation and severity of symptoms, and the drug's side-effect profile.20,21
Valproate and Divalproex: Valproate has demonstrated efficacy for bipolar disorder in several clinical trials,20 with an FDA indication for acute manic episodes. Valproate utilise should exist express to nonpregnant patients due to its tendency to crusade neural tube defects in the fetus.22,23
Dosing and Monitoring: The starting dose is 750 mg daily in divided doses, and should be titrated up to desired clinical effect. The goal is to reach therapeutic serum levels (fifty-125 mcg/mL), which generally occurs around ane,500 to 2,500 mg per day in divided doses.18,24 Valproate levels should be checked every six to 12 months in stable patients, or more oftentimes if clinically warranted.25
Side Effects: Mutual side effects include weight gain, airsickness, hair loss, easy bruising, and tremor. Divalproex may be used rather than valproate to decrease gastrointestinal discomfort. Hepatic failure, thrombocytopenia, and possible pancreatitis may occur with prolonged utilize; therefore, liver function, platelets, amylase, and lipase should be monitored every 6 to 12 months while the patient is on therapy, especially if symptoms of any of these furnishings arise.2,26,27
Lamotrigine: Lamotrigine has been shown to be more beneficial in patients affected by bipolar I disorder and in those who feel manic episodes than in bipolar II patients with hypomania.20,21 It has too been demonstrated in some clinical trials to be effective in bipolar II rapid cycling and every bit an offshoot in patients with bipolar low.28 In a unmarried blind comparing of lithium and lamotrigine monotherapy for the treatment of bipolar Ii depression, there was significant comeback of depressive symptoms from baseline in both groups, with no pregnant deviation between the two groups.29
Dosing and Monitoring: The starting dose is 25 mg daily for 2 weeks, 50 mg daily for 2 weeks, then titrated upwards by 50 mg weekly as clinically indicated, up to 200 mg daily.30 If used in combination with valproate, the dose of lamotri-gine should exist reduced past 50%, as these two agents are metabolized primarily via glucuronide conjugation and may compete for the same site of metabolism. In addition, valproate inhibits p-glycoprotein, which decreases the metabolism of lamotrigine.30
Side Effects: Side effects include rash and nausea, with more life-threatening adverse furnishings including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Carbamazepine: Carbamazepine may take some efficacy in managing bipolar II disorder; however, more than studies have been conducted with carbamazepine in the management of bipolar I manic and depressive episodes.xx
Dosing and Monitoring: The starting dose of carbamazepine is 100 to 200 mg once or twice daily, which should be increased by 200 mg per twenty-four hour period every ane to 4 days. The dose may be increased based on severity of symptoms and patient tolerance. The optimal dose is 800 to 1,000 mg per solar day in divided doses.18,31 Circumspection should be exercised when using carbamazepine with other medications metabolized via the CYP450 system, as it may induce the metabolism of other drugs as well as its own metabolism. This justifies the slow increase in dose as therapy continues.two,26,27
Side Effects: Side effects include nausea, vomiting, diarrhea, hyponatremia, rash, pruritus, leukopenia, fluid retention, and neurotoxicity, which may manifest as drowsiness, dizziness, and changes in vision, lethargy, and headache. Carbamazepine has also been associated with Stevens-Johnson syndrome and toxic epidermal necrolysis, which is more than common in patients who have the HLA-B*1502 allele, seen prevalently in South Asian populations.32-34
Antipsychotics
Some outset- and second-generation antipsychotics take demonstrated efficacy in patients with mania, moderate-to-astringent hypomania, and mixed states either as monotherapy or in combination with lithium, valproate, or carbamazepine.7-nine,35-39 Haloperidol has been widely used for mania and mixed states, more so for patients with bipolar I than for bipolar Two.xl,41 Olanzapine has been used as a first-line amanuensis as monotherapy or adjunct therapy because it has been shown to exist effective for acute mania, depressive episodes, and maintenance of patients with bipolar I disorder.1,42 Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are each similarly efficacious in treating acute mania, moderate-to-severe hypomania, and mixed states.7,8,35-37
The biggest business concern with the use of atypical antipsychotics is their tendency to crusade metabolic syndrome, which is characterized by weight proceeds, glucose intolerance, diabetes mellitus, and hyperlipidemia.1 Metabolic syndrome is more pronounced with olanzapine, risperidone, and quetiapine when compared with aripiprazole and ziprasidone. Patients taking these drugs should exist regularly monitored for weight, waist circumference, blood force per unit area, 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.i Refer to Tabular array ane for dosing and side furnishings.
Antidepressants
Few studies have shown promise for use of antidepressants in managing depressive symptoms in bipolar Ii disorder. A minor prospective study (88 patients) has shown that fluoxetine monotherapy may be an effective short-term handling (up to fourteen weeks) of bipolar II major depressive episode with a relatively low charge per unit of syndromal hypomanic episodes.43 Another randomized, double-blind, placebo-substituted trial compared long-term (50 weeks) fluoxetine, lithium monotherapy, and placebo.44 Lithium and fluoxetine both showed superiority to placebo. Results suggested fluoxetine monotherapy may provide relapse-prevention benefit relative to lithium monotherapy afterwards recovery from bipolar Two major depressive episode without an increase in hypomanic mood conversion episodes.44 Refer to Tabular array one for dosing and side effects.
The Part of the Pharmacist
The pharmacist plays a tremendous function in optimizing care for patients with bipolar 2 disorder. To clinical pharmacists, obtaining an authentic and complete medication history is very important in determining the appropriate therapy, or even identifying underlying medication-related causes of disease cycling. The chemist can be a viable component in providing appropriate dosing strategies, reviewing therapeutic regimens for drug interactions, instituting clinical monitoring parameters, and identifying signs and symptoms of medication toxicity. Clinical pharmacists can also provide the patient with discharge counseling. Educating this population on appropriate administration times, possible agin reactions, and potential drug interactions can increase medication adherence and reduce time to come hospitalizations.
Every bit an easily accessible resource, customs pharmacists are besides key players in providing optimal care to patients with bipolar II disorder. Not all institutions employ the services of a chemist for belch counseling, and in this case outpatient counseling through customs pharmacists is very of import in increasing medication compliance and adherence. Community pharmacists may also provide information most ways to identify early on signs and symptoms of mania or depression then as to aid patients seek medical aid sooner.
Conclusion
Bipolar Ii disorder is characterized by hypomanic episodes alternating with major depressive episodes without mania or psychosis. It is less debilitating than bipolar I disorder, yet it still has significant morbidity and mortality if left untreated. At that place are few studies that focus on treatment of bipolar II lone. The literature shows lithium to exist the mainstay of therapy to stabilize mood, forth with anticonvulsants (eastward.m., valproate, lamotrigine, or carba-mazepine) as adjunct therapy. More research and clinical trials are warranted.
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