Bipolar disorder treatment: medication dosages and treatment plans

Medically reviewed: 27, January 2024

Bipolar Disorder Treatment With Drug Therapy: A Comprehensive Overview

Bipolar disorder, previously known as manic depression, is a mental health condition characterized by extreme mood swings ranging between emotional highs (mania or hypomania) and lows (depression). These intense mood shifts can significantly impact energy levels, sleep patterns, judgment, behavior, and the ability to perform everyday tasks.

While there is no cure for bipolar disorder, appropriate treatment—which often includes drug therapy—can manage symptoms and enable individuals to lead fulfilling lives. In this article, we delve deeper into understanding how medication helps treat bipolar disorder, discuss various classes of drugs used, and shed light on possible side effects.

Effective pharmacological treatments for bipolar disorder aim at stabilizing mood fluctuations, minimizing severe depressive and manic episodes, improving daily functioning, reducing suicide risk, and enhancing overall quality of life. Several types of medications come into play when managing bipolar disorder symptoms, falling under distinct categories based on mode of action and primary therapeutic targets. These broad groupings encompass mood stabilizers, antipsychotics, antidepressants, and specific bipolar disorder medications.

1. Mood Stabilizers

Mood stabilizers form the cornerstone of drug therapy for bipolar disorder, given their efficacy in regulating mood swings across both poles of the affective spectrum. They are typically employed during acute phases of illness and maintenance periods alike. Lithium carbonate, valproic acid (Depakote), lamotrigine (Lamictal), carbamazepine (Tegretol), and oxcarbazepine (Trileptal) represent some commonly prescribed mood stabilizers.

Lithium Carbonate

Introduced in the late 1940s, lithium remains a widely accepted first-line treatment option for individuals grappling with bipolar disorder. Its primary mechanism involves manipulation of intraneuronal signaling cascades, thereby influencing neurotransmitter release and reuptake dynamics responsible for maintaining mood homeostasis. Research suggests that lithium interacts directly with glycogen synthase kinase-3 beta (GSK-3β), an enzyme implicated in various cellular functions, ultimately promoting neuronal survival and integrity.

Moreover, lithium has been found instrumental in inhibiting inositol monophosphatase (IMPase), leading to reduced concentrations of crucial secondary messengers involved in signal transduction processes integral to proper brain function. Collectively, these mechanisms endow lithium with remarkable mood-stabilizing properties, thus explaining its prominence within clinical settings.

It’s worth noting that patients commencing lithium treatment must undergo routine blood tests due to its narrow therapeutic index —the difference between therapeutic and toxic dosages being relatively small compared to many other medications. This necessitates meticulous monitoring to prevent potential adverse effects such as tremors, diarrhea, polyuria (excessive urination), polydipsia (excessive thirst), cognitive impairments, weight gain, and thyroid dysfunction. Furthermore, individuals should stay well hydrated throughout treatment duration since lithium excretion predominantly occurs through the kidneys, increasing susceptibility to nephrogenic diabetes insipidus (NDI), a rare yet serious complication marked by excessive fluid intake and polyuria resulting from compromised renal water handling capabilities.

Valproic Acid (Depakote)

Valproic acid belongs to a category of compounds collectively termed histone deacetylase inhibitors (HDACis), substances capable of modifying gene expression profiles at epigenetic levels. Specifically targeting GABAergic neurotransmission, valproic acid enhances GABA synthesis while simultaneously suppressing catabolism, culminating in elevated extracellular GABA concentrations conducive to dampening overactive limbic circuits instigative of affective disturbances observed in bipolar disorder.

Like lithium, valproic acid requires consistent blood level surveillance owing to a narrow therapeutic range associated with increased likelihood of encountering untoward reactions—particularly hepatotoxicity (liver damage) and pancreatitis (inflammation of the pancreas). Other potential side effects may manifest as nausea, dizziness, somnolence (sleepiness), alopecia (hair loss), and teratogenicity (ability to cause birth defects), underscoring the paramount importance of rigorous patient education prior to initiation of therapy.

Lamotrigine (Lamictal)

In contrast to traditional mood stabilizers acting primarily through ion channel blockade or second messenger interference, lamotrigine exhibits unique glutamatergic antagonistic properties targeted towards voltage-dependent sodium channels, thereby attenuating aberrant excitatory transmission presumed influential in propagating affective symptomology characteristic of bipolar disorder. By curbing pathologically augmented glutamatergic tone, lamotrigine fosters enhanced neural plasticity, bolsters neuroprotective defenses, and promotes restoration of optimal functional connectivity among disparate corticolimbic networks.

Although generally regarded as well tolerated, initial titration schedules mandate cautious implementation due to heightened risk of inducing cutaneous adverse events—namely Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)—potentially fatal conditions entailing widespread dermal sloughing precipitated by immune-mediated cytotoxic responses against keratinocytes (cells constituting outermost skin layers). Therefore, healthcare providers must remain vigilant during dose escalation stages, closely observing for emergence of early signs suggestive of SJS/TEN development (e.g., flu-like symptoms accompanied by mucocutaneous eruptions) to facilitate timely intervention and forestall progression toward irreversible sequelae.

Antipsychotic Medications as Bipolar Disorder Treatment

Antipsychotic agents—once traditionally reserved for schizophrenia management—have garnered considerable attention within bipolar disorder treatment research circles attributable to their demonstrated efficacy vis-à-vis affective regulation. Some prominent examples include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify), ziprasidone (Geodon), and lurasidone (Latuda). Notably, these drugs possess dual serotonin-dopamine antagonist attributes conferring them advantageous prospects as adjunctive treatments alongside conventional mood stabilizers or monotherapy alternatives depending on individual presentation severity and complexity.

While sharing overlapping neurological substrates underlying putative mechanisms responsible for therapeutic benefit, each compound harbors distinctive affinity profiles pertaining to respective receptor populations, engendering varying propensities for experiencing particular side effects.

For instance, certain antipsychotics (e.g., clozapine, olanzapine) exhibit pronounced propensity for provoking substantial weight gains and metabolic derangements warranting stringent cardiovascular risk assessment before and throughout treatment course. Consequently, judicious consideration should factor into clinicians’ decision-making calculus when selecting ideal candidates tailored to meet idiosyncratic needs and preferences whilst minimizing collateral harm.

Antidepressant Drugs for Bipolar Disorder Treatment

Despite compelling evidence affirming the utility of select antidepressants for treating major depressive episodes accompanying bipolar disorder, concerns persist regarding potential exacerbation of manic or hypomanic states following administration, particularly amongst those predisposed to rapid cycling pattern variants. Nonetheless, fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), and bupropion (Wellbutrin) belong to frequently utilized antidepressants in conjunction with mood stabilizer coadministration strategies aimed at tempering euphoric escalations amidst concurrent improvement of melancholic symptoms.

However, balancing risks versus benefits becomes paramount in negotiating suitable pharmacotherapeutic trajectories considering inherent vulnerabilities to developing treatment resistance, destabilizing switch phenomena, or sustenance of residual affective distress lingering beyond remission milestones. Collaborative efforts between patients and healthcare professionals remain indispensable tools in discerning optimal approaches aligned with personal circumstances and informed choices reflective of shared deliberation and consensus building.

4. Specialized Medications

Lastly, specialized medications specifically designed for bipolar disorder management occupy a burgeoning segment within psychiatric pharmacopeias. Examples comprise Symbyax—a combination product incorporating olanzapine and fluoxetine—and FDA-approved Quentiapine extended-release tablets (Seroquel XR).

Both products serve dual roles as acute phase episode controllers spanning unipolar and bipolar spectra whilst doubling as ongoing prophylaxis options aimed at preventing future recurrence. However, owing to comparable efficacies reported between established mood stabilizers and novel entities coupled with higher acquisition costs, widespread adoption rates have remained comparatively modest despite promising clinical trial outcomes demonstrating statistically significant improvements in global assessments measuring psychopathological burden and general functionality domains.

Bipolar disorder, also known as manic-depressive illness, affects more than 10 million Americans according to the National Alliance on Mental Illness. The disorder is characterized by extreme changes in mood. The National Library of Medicine defines these extremes as manic, energetic highs and depressive lows.

Although the cause of bipolar disorder is unknown, it often runs in families. The disease may also be triggered by environmental and biological factors including sleep deprivation, hypothyroidism and certain medications. Typically, symptoms appear in older teens or individuals in their early twenties.

Bipolar disorder: common treatment options

Treatment with Medication

Medication is first prescribed to stabilize mood swings. Treatment following stabilization is aimed at maintaining mood balance and can include a single drug or a combination of drugs. Lithium has been around the longest and is indicated for the treatment of mania and depression. Side effects of lithium can be serious and include hypothyroidism, muscle weakness and slurred speech.

To prevent these side effects, physicians measure lithium levels in the blood. The frequency of these blood tests is determined by the doctor on a case-by-case basis. A newer medication, Symbyax, is composed of an antidepressant and an antipsychotic and can be used to stabilize mood. Serious side effects include suicidal thoughts, allergic reactions and a syndrome characterized by high fever, rigid muscles and convulsions. Anticonvulsants, antipsychotics (as a secondary option to anticonvulsants) and antidepressants are other options. Benzodiazepines, or anti-anxiety drugs, are sometimes prescribed on a limited basis to aid sleep.

Because of the complexity of the disease, the Mayo Clinic says that several medications must be tried until the best option is found.

Bipolar disorder Treatment with Therapy

In addition to medication, an integral part of bipolar disorder treatment is therapy. Several types of therapy exist but the most popular is cognitive behavioral therapy. According to the National Alliance on Mental Illness, behavioral therapy can be as effective as antidepressant drugs.

Through behavioral therapy, patients learn to recognize harmful behaviors and unhealthy thinking that may lead to mood changes. Then, they are taught how to replace those behaviors with healthy alternatives.

Psychologists say that cognitive behavioral therapy trains patients to deal with stress. Family and group therapy are sometimes recommended to educate the patient’s family about the disease, help patients communicate better, and prevent patterns that may have triggered manic-depressive episodes in the past.

A small number of patients may undergo electroconvulsive therapy if mood swings become more severe or if other treatments have proven ineffective. The Mayo Clinic defines electroconvulsive therapy as electrical currents passing through the brain. The shock to the brain may change brain chemistry and improve a patient’s mood.

Bipolar treatment Treatment with Lifestyle Changes

Patients with bipolar disorder can also make lifestyle changes that can help prevent future manic-depressive episodes. Many doctors recommend frequent exercise because a good work out releases “feel good” chemicals called endorphins in the brain.

Endorphins not only improve mood but also sleep, which helps stabilize mood. Other recommendations include avoiding alcohol and illegal drugs as well as relationships that promote this type of behavior.

Here is the detailed treatment plan for the patients with bipolar disorder.

Bipolar affective disorder: clinical guidelines, treatment protocols

Relief therapy for manic states (MS). Tactics and stages of pharmacotherapy for MS

First choice therapy

All patients diagnosed with MS are recommended to undergo pharmacotherapy to relieve symptoms and achieve remission.

When treating bipolar disorder, for all patients, in order to quickly relieve current psychopathological symptoms and subsequently maintain the euthymic period, it is recommended to perform three mandatory stages: relief therapy, after-treatment (maintenance) therapy and preventive (anti-relapse) therapy.

The treatment strategy for MS in bipolar disorder is based on the subsequent preventive stage. A gradual relief of MS is recommended, taking into account the severity (mild, moderate, severe) and the type of manic syndrome: cheerful (euphoric) mania, angry (dysphoric) mania, mania with psychotic features (manic-delusional state).

The choice of therapy for the relief of MS is determined not only by the characteristics of the action of various groups of drugs, but also by their tolerability. It is possible to significantly increase the effectiveness of therapy by following certain methodological rules for its implementation. Adequate dosage and dynamic and timely changes in therapy allow you to quickly relieve symptoms and prevent the episode from prolonging. It should also be taken into account that the prescription of a drug for maintenance normotimic therapy (lithium salts, antiepileptic drugs, second-generation antipsychotics (SGAs) (except for lurasidone, which is not approved for medical use to relieve MS) should be carried out quite early and “superimposed” on the initial stage relief therapy, since the preventive effect of these drugs develops relatively slowly.

The use of SGAs in most cases is preferable to first-generation antipsychotics (FGAs), primarily due to their better tolerability (less pronounced sedation, risk of extrapyramidal symptoms (EPS), risk of hyperprolactinemia, depressogenic effect, risk of phase inversion). In addition, it is known that in patients with affective disorders, EPS when using anticholinergic drugs develop several times more often than in patients with schizophrenia, which requires the additional addition of anticholinergic drugs.

Goal of therapy: achieving remission (for a more accurate psychometric determination of remission, you can use the Young scale, according to which the severity of symptoms should not exceed 10-12 points).

Therapy goals:

• the fastest possible relief of manic symptoms;
• rapid control of psychomotor agitation and aggressiveness;
• preventing the development or intensification (in mixed conditions) of depressive symptoms;
• selection of drugs taking into account individual tolerance for subsequent long-term preventive use.

The treatment plan for manic states is based on an analysis of the patient’s status, anamnesis data and the dominant polarity of the course of the disease.

For patients with cheerful (euphoric) mania at the initial stage of treatment for MS or hypomania, monotherapy with one of the drugs with a normotimic effect is recommended: lithium carbonate, valproic acid or SGA.

For patients with angry mania at the initial stage of therapy for MS or hypomania, monotherapy with one of the drugs that has a normotimic effect is recommended:

• valproic acid,
• carbamazepine,
• or WUA.

The choice of a drug for relief therapy should be carried out taking into account the subsequent preventive stage of therapy and take into account the patient’s individual tolerance of the selected drug during long-term use. Valproic acid is preferred over lithium carbonate (valproic acid does not require regular monitoring of plasma concentrations and has a more favorable side effect profile).

Other anticonvulsants (carbamazepine, oxcarbazepine, topiramate, gabapentin and calcium channel blockers can be used for alternative therapy. It is not recommended to prescribe haloperidol at the first stage of MS relief, except in cases of severe psychomotor agitation and/or severe anger and aggressiveness.

• Oxcarbazepine dosage regimen:

the initial dose is 600 mg/day (8–10 mg/kg body weight per day), divided into two doses. The dose is increased by no more than 600 mg/day at intervals of approximately 1 week until the desired therapeutic effect is achieved. Dose range 600–1200 mg/day.

• Topiramate dosage regimen:

the minimum effective dose is 200 mg/day. Typically, the total daily dose is from 200 mg to 400 mg and is taken in 2 divided doses. Some patients may need to increase the daily dose to a maximum of 1600 mg. It is recommended to start treatment with a low dose, followed by gradual selection of an effective dose. Dose selection begins with 25-50 mg, taking them at night for 1 week.

In the future, at intervals of 1-2 weeks, the dose can be increased by 25-50 mg and taken in 2 doses. When selecting a dose, it is necessary to be guided by the clinical effect. In some patients, the effect can be achieved by taking the drug once a day.

• Clozapine dosage regimen:

Clozapine should be used only if the leukocyte count and absolute neutrophil count are within the normal range before treatment. In addition, when using the drug, it is necessary to regularly determine the number of leukocytes and the absolute number of neutrophils. The dose of the drug is determined individually. For oral administration, a single dose is 50-200 mg, daily – 200-400 mg. Treatment is usually started with a dose of 25-50 mg, then gradually increased by 25-50 mg per day to 200-300 mg/day over 7-14 days. The daily dose can be used once before bedtime or 2-3 times a day after meals. If treatment is discontinued, the dose should be gradually reduced over 1-2 weeks.

Therapeutic strategies for failure of pharmacotherapy

For patients in whom drug therapy has proven ineffective, it is recommended to use non-drug treatment methods: electroconvulsive therapy (ECT) or special anti-resistant measures (plasmapheresis, immunomodulators, calcium channel blockers, etc.).

ECT is recommended to be performed 3 times a week until the symptoms of mania subside. Typically three to six ECT sessions are performed. MS is considered resistant if after 6-10 ECT sessions the symptoms are not relieved.

Maintenance therapy for manic states

After relief of acute MS, it is recommended for all patients to proceed to the stage of condition stabilization (follow-up treatment) in order to reduce residual symptoms, prevent the development of phase inversion and achieve stable remission.

After relief of acute MS, for all patients at the stage of stabilization (follow-up treatment), it is recommended to continue normothimic therapy or a combination of drugs for 3-4 months, gradually reducing or eliminating sedative antipsychotic therapy, APPs and benzodiazepines, the constant use of which is not recommended for more than 1-2 months. -for their high addictive potential.

• For patients with ongoing lytic reduction of symptoms, further normothimic therapy in combination with SGAs is recommended.
• For patients taking a combination of normotimic therapy and SGAs, if remission is maintained for 3-4 months, it is recommended to transfer to long-term maintenance monotherapy with the drug that achieved the greatest effect and was well tolerated.
• In patients who experience early relapse during the dose reduction period or immediately after discontinuation of SGAs, resumption of combination therapy is recommended.

Management of a patient with MS with severe psychomotor agitation and aggressiveness

Agitation, as well as manifestations of aggression, are quite often a separate problem in the treatment of patients with angry mania, mania with mixed features and mania with psychotic symptoms. Aggression in manic patients is usually directed at random individuals, and can be unmotivated or provoked by unimportant factors: comments made, restrictions, unfriendly views.

Also, a provoking factor may be conflicts associated with the refusal to fulfill the inadequate demands of a patient with a manic state. At the same time, aggression in psychotic mania develops within the framework of disorganized behavior and can be caused by deceptions of perception or delusional symptoms. In case of mania, in contrast to patients with schizophrenia, a high risk of aggression remains in the hospital after hospitalization.

Bipolar Disorder Therapy for agitation and aggression

At the first pre-psychopharmacological stage of managing a patient with manifestations of agitation, the use of de-escalation techniques is recommended.

De-escalation techniques include several components simultaneously. First of all, it involves continuous risk assessment and monitoring of the situation while simulating a safe environment around the patient. An indispensable condition is maintaining a safe distance for the patient and staff, avoiding provocations and coercion, treating the patient with respect, showing empathy, and identifying the patient’s needs. Attempts to distract the patient, rethink the situation, establish verbal contact, negotiations and persuasion are also necessary.

Oral, buccal (orodispersible tablets) psychopharmacotherapy is recommended as a first step, subject to the possibility of its use (compliance).

Caution is recommended when prescribing diazepam and other benzodiazepine derivatives (except lorazepam), as well as low-potency antipsychotics (chlorpromazine, levomepromazine and chlorprothixene) to patients with psychomotor agitation for the treatment of agitation due to poorer tolerability and longer half-life.

If agitation is not severe and the patient is compliant, oral forms of drugs with a sedative component may be more preferable. In this case, benzodiazepine derivatives (primarily lorazepam), promethazine and antipsychotics demonstrate comparable effectiveness in the treatment of agitation and aggression. At this stage of therapy, the patient requires observation every hour.

Scheme of use of lorazepam (for oral administration): initial dose – 2-3 mg / day, divided into 1-3 doses. Gradually, the dose can be increased to a maximum of 10 mg/day.

For patients with acute psychomotor agitation, when oral therapy is ineffective or impossible to use, as well as with the initial severity of symptoms, parenteral therapy is recommended.

Parenteral forms of SGAs are not inferior in effectiveness to the intramuscular form of haloperidol, but cause fewer neurological side effects.

Therapeutic approaches for agitation and aggression should be differentiated. Manifestations of aggression, as well as conditions with a high risk of its development, require urgent therapeutic measures. These include the use of rapid tranquilization (RT) and, if necessary, restraint or isolation. Along with this, it is necessary to use behavioral therapy techniques. In cases of mild manifestations of aggression (verbal aggression, etc.), BT may not be appropriate. When conducting BT, skills are required to assess the risks associated with the possible achievement of deep sedation (development of arterial hypotension and respiratory depression). It is also desirable to provide the technical means necessary for urgent assistance in the development of side effects, including the possibility of prescribing flumazenil (an antidote, according to the mechanism of action – a benzodiazepine receptor antagonist).

At the beginning of therapy, drugs should be prescribed in the lowest effective dosages, which, if necessary, can be gradually increased. More severe forms of agitation require the use of parenteral therapy. When relieving agitation, it is desirable that the therapeutic effect be achieved at the level of sedation or light sedation. If necessary, in cases of severe intractable agitation with manifestations of aggression, deep sedation or even anesthesia is allowed. The use of BT for arousal control is considered as a last line treatment. However, in cases of extremely severe agitation associated with risks of aggression, it should be used immediately.

Combined intramuscular psychopharmacotherapy is recommended for patients with psychomotor agitation when intramuscular monotherapy is ineffective.

When using this combination, it is necessary to take into account the increased risk of side effects, which requires constant monitoring of the patient. Combinations of haloperidol with benzodiazepine derivatives are usually used – primarily lorazepam (2-4 mg/day orally) or promethazine is recommended.

Promethazine dosage regimen: When administered intramuscularly, care should be taken to avoid accidental subcutaneous administration, which may cause tissue necrosis at the injection site. The usual recommended dose is 25-50 mg deep intramuscularly.

• The combined use of the intramuscular form of benzodiazepine derivatives with clozapine should be avoided due to the risk of developing respiratory failure.
• The combined use of intramuscular olanzapine and benzodiazepine derivatives should be avoided due to the increased risk of sudden death.
• If combined parenteral intramuscular therapy is ineffective to relieve psychomotor agitation in patients with psychomotor agitation, intravenous administration of benzodiazepine derivatives (diazepam, bromodihydrochlorophenylbenzodiazepine) or antipsychotics (haloperidol, chlorpromazine, droperidol) is recommended.

When using the intravenous route of administration, the drip method is preferred. When administering drugs intravenously, constant monitoring of personnel at the patient’s bedside, monitoring of ECG, blood pressure and saturation are required. With intravenous use of droperidol (2.5-10 mg/day), due to the risk of prolongation of the QT interval, ECG monitoring is strictly necessary. These requirements are feasible in an intensive care unit.

In case of resistant psychotic agitation, subsequent therapeutic steps are taken collectively, including with the involvement of specialists of other profiles (anesthesiologists-resuscitators and neurologists).
In this case, further management of the patient is carried out in a psychiatric intensive care unit. It is advisable to further examine the patient to possibly clarify the diagnosis. One of the main therapeutic options is the use of ECT, especially in the presence of affective symptoms, catatonic symptoms, and indications of its good effect in the past.

Consider dexmedetomidine and ketamine as alternative therapeutic options.

Relief therapy for depression in bipolar disorder

Tactics and stages of pharmacotherapy for bipolar depression (BD)

First choice therapy

All patients diagnosed with BD are recommended to undergo pharmacotherapy to relieve symptoms and achieve remission.

The goal of therapy is to achieve remission (for a more accurate psychometric definition of remission, you can use the Hamilton scale for assessing depression (Appendix D4), according to which the severity of symptoms should not exceed 7 points, or the Montgomery-Asberg scale (Appendix D6), according to which remission is determined when symptom score below 10 points).

Therapy goals:

• the fastest possible relief of depression symptoms,
• preventing suicide attempts,
• prevention of phase inversion (development of manic symptoms).

The treatment plan for BD is based on an analysis of the patient’s clinical status, anamnesis data and the dominant polarity of the course of the disease.

When deciding whether to receive inpatient or outpatient treatment, it is important to consider:

• severity of the condition,
• suicide risk,
• presence or absence of psychotic symptoms,
• anamnestic data,
• conditions of the microsocial environment and the degree of participation of loved ones in the therapeutic process.

Hospitalization is mandatory in the presence of suicidal risk and/or psychotic symptoms.

Therapeutic tactics for depressive phases within the framework of bipolar disorder I and bipolar disorder II do not differ significantly, however, the choice of drug is recommended taking into account:

• the predominant polarity of affect during the course of the disease,
• severity of the condition and clinical variant of depression,
• presence/absence of mixed traits,
• the effectiveness of a particular drug in relieving previous depression, as well as the risk of phase,
• inversion.

In all cases, when treating BD, it is recommended to avoid the use of tricyclic antidepressants (TCAs) and classical antipsychotics. In case of severe anxiety, alimemazine may be added to the main treatment regimen.

When combining anticonvulsants, drug interactions at the level of liver enzymes must be taken into account. Thus, valproic acid increases the serum concentration of lamotrigine, so it is recommended to adjust the dosage of the latter and use a slower titration. Carbamazepine accelerates clearance, reduces the concentration of sodium valproate in the blood and potentiates toxic effects on the liver, and therefore this combination is undesirable.

All patients with mild or moderate BD undergoing pharmacotherapy are recommended to undergo cognitive behavioral and other types of psychotherapy.

For mild depression, such a correction of therapy is often sufficient to achieve an effect. The most important factor for achieving success in the management of patients with mild and moderate depression is also the rapid normalization of sleep disorders and the correction of chronobiological disorders.

First-line treatment for Bipolar Disorder type 1 without psychotic symptoms

For all patients diagnosed with type 1 BD without psychotic symptoms, one of the following therapeutic options is recommended in order to relieve symptoms and achieve remission:

• quetiapine
• lithium carbonate
• Lithium carbonate dosage regimen:

the dose is determined by the level of lithium concentration in the blood plasma. The therapeutic concentration of lithium in plasma is 0.6-1.0 mmol/l. Taken orally, for adults the dose is 300-600 mg 3 times a day. The concentration of lithium in blood plasma should not exceed 1.2 mmol/l.

• lamotrigine
• lurasidone
• cariprazine
• combination of lurasidone with lithium carbonate or valproic acid

If the patient is already taking normotimic therapy for preventive purposes, relief of depression is carried out against the background of the normotimic therapy being taken.

Treatment strategies for type 1 BD without psychotic symptoms when first-line therapy is ineffective

For patients with an established diagnosis of type I BD without psychotic symptoms, if first-choice therapy is ineffective in order to relieve symptoms and achieve remission, it is recommended to use one of the unused first-stage options.

As another option, patients with an established diagnosis of type 1 BD without psychotic symptoms, if first-choice therapy is ineffective, are recommended to use a combination of normotimic therapy and first-choice SGA.

Among antiepileptic drugs, taking into account the subsequent preventive stage of therapy, if manic phases predominate during the course of the disease, it is recommended to give preference to valproic acid, and for depressive phases, lamotrigine. The evidence base for carbamazepine is worse; its use in BD is justified only if the patient is already taking this drug as a preventive therapy.

• Carbamazepine dosage regimen:

initiation of therapy – 200 mg/day, followed by dose increase under control of effectiveness and tolerability to 600-1200 mg/day.

For patients with an established diagnosis of type 1 BD without psychotic symptoms and ineffective treatment of the first and second stages in order to relieve symptoms and achieve remission, it is recommended to use one of the following therapeutic options:

• valproic acid
• combination of valproic acid with blood pressure from the SSRI group
• combination of lithium carbonate with blood pressure from the SSRI group
• combination of SGAs with blood pressure from the SSRI group
• combination of olanzapine and fluoxetine

Dosage regimen for the combination of olanzapine and fluoxetine: the initial dose is 5 mg of olanzapine and 20 mg of fluoxetine per day. Lower starting dosages should be used in patients prone to hypotension or potentially slow metabolizers. Dosages are increased depending on effectiveness and tolerability. The safety of dosages higher than 18 mg of olanzapine in combination with 75 mg of fluoxetine has not been studied.

ECT treatment for bipolar disorder

Data support the effectiveness of short-pulse right unilateral placement, although the data are insufficient to decide on unilateral or bilateral electrode placement for ECT use in bipolar depression.

For patients diagnosed with type 1 BD without psychotic symptoms, in whom the above therapeutic measures were ineffective, it is recommended to add one of the following therapeutic options:

• aripiprazole

The initial dose of aripiprazole is 5-10 mg/day, usually at night, and over the course of a week, depending on the effect and tolerability, the dose is gradually increased by 5-10 mg/day to a maximum dose of 30 mg/day.

• carbamazepine in doses of 400-1000 mg/day
• eicosapentaenoic acid (dietary supplement)

Eicosapentaenoic acid is one of several omega-3 polyunsaturated fatty acids (omega-3 triglycerides), doses vary from 2 to 10 g/day.

• light therapy
• levothyroxine sodium

Dosage regimen – 300 mcg once a day 20-30 minutes before meals.

• acetylcysteine

Dosage regimen – 2 g/day in addition to the ongoing treatment.

• olanzapine

Dosage – 5-20 mg/day.

• transcranial magnetic stimulation to the area of the left or right dorsolateral cortex.
• SSRIs or monoamine oxidase inhibitors (type A) (MAOIs).

When choosing blood pressure, preference should be given to selective serotonin reuptake inhibitors (SSRIs). The addition of blood pressure to normotimic therapy may be justified for depression within the framework of bipolar disorder I and bipolar disorder II in patients with a positive effect of blood pressure therapy in the anamnesis.

If the structure of depression contains mixed features (2 or more manic symptoms) or if the patient has a history of phase inversions when using AD, their addition is contraindicated. Monotherapy for AD should be avoided due to the high risk of phase inversion and increased phase formation and aggravation of the course of the disease as a whole. If blood pressure is prescribed, it is necessary to carefully monitor the appearance of signs of hypomania/mania or psychomotor agitation; if they appear, blood pressure should be discontinued.

For patients with BD who do not have a history of BC or a manic episode immediately preceding the present depression, after relief of depressive symptoms, taking AD in combination with normotimic therapy can continue for up to 6-12 weeks to relieve residual symptoms and achieve stable remission.

If there is a history of CD or a current episode of depression was immediately preceded by a manic state, after relief of depressive symptoms, blood pressure should be discontinued as early as possible, already from the second week after achieving clinical remission. In all circumstances, it is advisable to gradually reduce the dose (25-33% every 2-4 days). In case of relapse of depression during the period of dose reduction or immediately after discontinuation of blood pressure, it is recommended to resume the relief therapy regimen.

Despite the need to limit the period of blood pressure use, approximately 20% of patients with bipolar disorder require blood pressure maintenance therapy. For patients with frequent relapses of depression that develop as a result of drug withdrawal, they can be recommended for a long term as part of a preventive therapy program.

First-line treatment strategies for severe type 1 bipolar disorder with psychotic features

All patients diagnosed with severe BD with psychotic features are recommended to be prescribed a combination of normothymic therapy with SGAs in order to relieve symptoms and achieve remission.

Treatment strategies for severe bipolar disorder – type 1 with psychotic symptoms when first-choice prescriptions are ineffective

For patients diagnosed with severe BD with psychotic features, in whom the above therapeutic measures were ineffective, it is recommended to prescribe unused first-choice options or a combination of normotimic therapy with FGAs.

In some clinical cases, it is possible to prescribe FGAs, however, due to the predisposition of patients with bipolar disorder, especially during periods of depression, to the development of neurological side effects, preference should be given to FGAs.

Patients diagnosed with type 2 bipolar disorder with psychotic symptoms and insufficient effectiveness of pharmacotherapy in order to relieve symptoms and achieve remission are recommended to use ECT.

Patients diagnosed with type 2 BD with psychotic symptoms and insufficient effectiveness of all of the above methods in order to relieve symptoms and achieve remission are recommended to use any of the methods listed above for relieving bipolar disorder.

Bipolar Disorder Therapy for mixed affective episode or mixed state (MS)

At all stages of CC therapy, the selection of the optimal therapeutic dose is carried out taking into account the patient’s individual sensitivity to the drug. If it is impossible to use adequate dosages due to the development of side effects, it is recommended to switch to another drug from those listed for this stage of therapy.

The duration of therapy with first-choice drugs is at least 2-4 weeks. If the patient has a partial effect, treatment can be continued for another 4 weeks or drugs in the second stage of therapy can be prescribed. If there is no effect after 4 weeks of therapy with first-choice drugs, you need to move on to the second stage of therapy.

First-choice treatment for SS with predominant depressive symptoms (Mixed depression (MD))

Ziprasidone is recommended for all patients diagnosed with diabetes in order to relieve symptoms and achieve remission. Ziprasidone has only been studied in mixed conditions within type 2 bipolar disorder. The question of whether these data can be unconditionally extrapolated to type 1 bipolar disorder remains controversial. However, at the moment, more conclusive studies with positive results in diabetes have not been conducted for other drugs.

If the patient is already taking normotimic therapy for prophylactic purposes, relief therapy for diabetes and the prescription of ziprasidone is carried out against its background.

Strategies for treating diabetes when first-line therapy is ineffective

For patients with an established diagnosis of diabetes who received ziprasidone at the first stage of relief therapy without sufficient effect, it is recommended that in order to relieve symptoms and achieve remission, the following is prescribed:

• olanzapine as monotherapy or in combination with fluoxetine
• or carbamazepine
• or lurasidone
• or ECT

If the prescribed drug is ineffective, it is necessary to switch to prescribing an unused option. In cases where the patient is already receiving normotimic therapy for prophylactic purposes, it is recommended to carry out reversing therapy for diabetes along with the intake.

First choice therapy for SS with predominant manic symptoms (mixed mania (MS))

In order to relieve symptoms and achieve remission, it is recommended that all patients with an established diagnosis of SM be prescribed olanzapine, ziprasidone or cariprazine.

For patients with an established diagnosis of SM who are already receiving normotimic therapy, it is recommended that olanzapine or ziprasidone be added to relieve symptoms and achieve remission.

Bipolar Disorder Treatment strategies for SM when first-line therapy fails

For patients with an established diagnosis of SM who received olanzapine at the first stage of relief therapy without sufficient effect, it is recommended that olanzapine be prescribed in combination with valproic acid or monotherapy with aripiprazole or paliperidone in doses of 3-12 mg/day or quetiapine + normothymic therapy in order to relieve symptoms and achieve remission.

If the prescribed drug is ineffective, it is necessary to switch to prescribing an unused option. In cases where the patient is already receiving normotimic therapy for prophylactic purposes, it is recommended that reversing therapy for SM be carried out against the background of the normotimic therapy being taken). To correct anxiety symptoms, alimemazine can be added to the main treatment regimen.

Strategies for treating SM when second-choice therapy is ineffective

For patients with an established diagnosis of SM, for whom drugs in the second stage of therapy turned out to be ineffective, it is recommended to prescribe one of the following drugs:

• clozapine in doses of 200-900 mg/day
• gabapentin in doses of 300-900 mg/day (maximum dose studied – 4800 mg/day) + normothymic therapy
• oxcarbazepine (600-1200) + lithium carbonate
• risperidone (1-6 mg/day)
• AMS
• ECT

If the prescribed drug is ineffective, it is recommended to switch to prescribing an unused option. In cases where the patient is already receiving normotimic therapy for preventive purposes, reversing therapy for SM should be carried out against the background of the normotimic therapy being taken.

Conclusion

Bipolar disorder is a complex mental health condition necessitating multifaceted treatment paradigms integrating diverse combinations of psychopharmaceuticals intended to target core dimensions of disease manifestation. Although no panacea exists for bipolar disorder, judicious employment of available drug therapies offers tangible relief to millions suffering worldwide.

Ongoing advancements promise brighter horizons heralding refined understanding of etiopathogenic processes fuelling disordered cognition and emotion, setting stage for tomorrow’s breakthrough discoveries accelerating translation from benchside innovations to bedside applications poised to revolutionize care delivery models shaping our collective futures.