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19FEATURES OF TREATMENT OF BIPOLAR AFFECTIVE DISORDER IN WOMEN OF FERTILE AGE
Ivanova N. M., psychiatrist, psychotherapist, assistant of the department Ukraine, Chernivtsi
Higher State Educational Institution of Ukraine "Bukovinian State Medical University" Departments of Nervous Diseases, psychiatry and medical psychology
DOI: https://doi.org/10.31435/rsglobal_ws/12072018/6032
ABSTRACT
Recent research in the field of mental disorders, in particular affective, is aimed at restoring the quality of life of patients, optimizing the provision of medical care and minimizing the side effects of drug treatment, especially in women of childbearing age, as well as preventing stigmatization. According to the recommendations in the clinical evaluation of bipolar affective disorder should pay special attention to comorbidity with other disorders of the axis 1 and 2 (according to DSM-V), family history of mental disorders, course of the disease, age of the patient at the time of the debut, frequency of phase changes, the presence of mixed episodes and seasonality. The purpose of therapy in acute affective episodes is to reduce the severity of symptoms, to achieve eutymium with the ultimate achievement of complete remission. The purpose of supportive therapy is to prevent relapses of affective episodes. Medicines used in treating patients with bipolar affective disorder include mood stabilizers (lithium salts, valproic acid salts, lamotrigine, carbamazepine) and atypical antipsychotics and antidepressants recommended by the FDA.
Citation: Ivanova N. M. (2018). Features of Treatment of Bipolar Affective Disorder in Women of Fertile Age. World Science. 7(35), Vol.4. doi: 10.31435/rsglobal_ws/12072018/6032
Copyright: © 2018 Ivanova N. M. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Introduction. The development of medical science and the expansion of opportunities for in-depth study of the peculiarities of mental disorders, as well as the emphasis of modern medical practice on restoring the quality of life of patients in the psychiatric group, give more and more attention to early diagnosis and effective methods of treatment of bipolar affective disorder. To improve clinical practice, a systematic combination of all diagnostic and therapeutic aspects is necessary, including a thorough study of anamnesis, all clinical manifestations (not only affective, but also cognitive, behavioral) and features of the course of the disease. Such an approach is due to the priority in helping primarily restoration of social functioning, an obstacle to which often becomes untreated cognitive impairment, the use of ineffective therapies.
The frequency of bipolar affective disorder in the general population, according to various authors, is very volatile, which is explained by a number of objective reasons: the discrepancies in determining the diagnostic boundaries of this form of pathology, the methods of statistical accounting of patients, a significant number of patients with so-called outpatient, cyclothymic, in that including hidden variants of the mentioned disorder, which are often not taken into account. Among the total number of hospitalized patients in the psychiatric hospital, patients with bipolar affective disorder are on average 2 to 6%. In the structure of mental illness, bipolar disorder is 1.6%, according to WHO.
ARTICLE INFO
Received: 13 May 2018 Accepted: 27 June 2018 Published: 12 July 2018
KEYWORDS
bipolar affective disorder; phases;
treatment approaches; fertility age; thimostabilizers
According to the results of large-scale research over the last 40-50 years, it has been possible to formulate a concept of the spectrum of bipolar disorder, according to which bipolar disorders constitute up to 50% of all mood disorders. The BAD spectrum, in addition to Bipolar I Disorder and Bipolar II Disorder, includes Bipolar III Disorder (cyclothymium) and Bipolar IV Disorder (recurrent episodes of depression and anti-depressant hypomania induced), variants of the course of depression and sub-depression with hyperthermia. There are also offers to consider as a separate type of Bipolar disorders recurrent depression accompanied by symptoms of dysphoria (angry mania - hypomania), variants of depression with late manifestation and symptoms dysphoria (flabby mania - hypomania), depression variants with a late manifestation and hypomanic symptoms that precede dementia, options for a hyperkinetic disorder with devastating behavior and a late manifestation after 6 years that do not respond to psychostimulant therapy. According to the recommendations in the clinical assessment of ADH should pay special attention to comorbidity with other disorders of the axis 1 and 2 (according to DSM-V), family history of mental disorders, course of the disease, age of the patient at the time of the debut, frequency of phase changes, the presence of mixed episodes and seasonality. For example, the early age of the manifestation correlates with the more severe course of the Bipolar disorders and the worse prognosis. Early onset of the disorder (< 21 years) is characterized by a more frequent occurrence of comorbid alcohol and drug dependence, obsessive-compulsive disorder, disorders of eating behavior, rapid phase change, more episodes, suicidal attempts, etc. The presence of comorbid psychiatric disorders is diagnosed in about 30% of patients with bipolar disorders. Their presence, as demonstrated by the results of research, is associated with more mixed and depressive episodes, suicidal attempts. In addition, comorbid psychiatric disorders are more common in people with depressive manifestation of bipolar disorders. Family burden for bipolar disorders and major depressive disorder is also of great predictive value.
In addition, comorbid psychiatric disorders are more common in people with depressive manifestation of bipolar disorders. Family burden for bipolar disorders and major depressive disorder is also of great predictive value with more mixed and depressive episodes, suicidal attempts.
Pharmacological treatment is the basis in the complex treatment of patients with bipolar disorders. The purpose of therapy in acute affective episodes is to reduce the severity of symptoms, to achieve eutymium with the ultimate achievement of complete remission. The purpose of supportive therapy is to prevent relapses of affective episodes. Medicines used in treating patients with bipolar disorders include mood stabilizers (lithium salts, valproic acid salts, lamotrigine, carbamazepine) and atypical antipsychotics and antidepressants. In tabl. 1 shows medicines approved by the Food and Drug Administration (FDA) for the treatment of various phases of bipolar disorders and supportive care.
Table 1. Medicines recommended by the FDA for BPA treatment
Acute affective episode Supportive treatment
Medicinal treatment manic depressive mixed
Mood stabilizers
Lithium salt M, C X M, C
Valproic acid salts, valproic acid salts ER M, C X X
Carbamazepini ER M, C M, C
Lamotrigine X M, C
Atypical antipsychotics
Aripiprazole M, A M, A M, A
Olanzapine M, A (with fluoxetine in BAD I) M, A M
Cvetiapine IR, XR M, A M (BAD I,II) M, A (only XR) A
Risperidone M, A M, A M, A (only RLAI)
Ziprazidone M M A
A - recommended for additional mood stabilizer therapy; C - recommended for combination therapy with another mood stabilizer, an atypical antipsychotic or antidepressant; M - recommended for monotherapy; RLAI (Risperidone long-acting injection) - prolonged-release risperidone in injections; X is recommended by international guidelines, consensus, but not approved by the FDA.
Research results: the main group of drugs for the treatment of bipolar disorders according to clinical protocols is thimostabilizers. Lithium is the first drug that has been shown to be effective in bipolar disorders. Despite a number of limitations (delayed therapeutic effect in acute mania, limited efficacy in the treatment of bipolar depression, the most severe attacks with psychotic symptoms, bipolar disorders with frequent phase changes (5-20% of patients), dysphoric and mixed manic conditions (20-40% of all affective episodes of bipolar disorders), schizoaffective disorders, affective disorders due to organic brain disease, manic episode in the elderly, patients with bipolar disorders and comorbidly addictive behavior, narrow therapeutic window), treatment with lithium salts remains relevant for modern clinical practice. During the last 10 years, when lithium is used, emphasis is placed on high efficacy in preventing recurrence of manic episodes, as well as the fact that it is the only medicinal product that has been shown to reduce the risk of suicide in bipolar disorders. The use of lithium salts in reduced doses to increase its tolerability has not proven effective.
Salts of valproic acid (valprocom, depakin) - mood stabilizers with the most evidence base. In the treatment of valproate sodium in acute mania, the therapeutic response is faster than when treating lithium salts. Valproic acid salts significantly outweighed the effectiveness of placebo in the treatment of manic episodes, placebo and lithium salts in the treatment of depressive episodes, episodes with rapid phase change, more effective than placebo in the prevention of mania.
In placebo-controlled trials, carbamazepine has been shown to be effective in acute mania and mixed conditions. The evaluation of the efficacy of carbamazepine in monotherapy and polytherapy in the open-ended (on average 10 years) of a naturalistic study (Chen C.H, Lin S.K, 2012) demonstrated its efficacy in most patients (48.8% of randomized patients did not have affective disorders during the controlled period). In a significant proportion of patients with BAD to achieve eutymic and correction of psychomotor excitation in manic and mixed affective disorders, with carbamazepine, additional antipsychotic therapy (68.2%) and benzodiazepines (74.4%) were used.
A number of studies have confirmed the presence of teratogenic effects of valproic acid salts, carbamazepine and lithium salts (Dodd S., Berk M., 2004; Tatum W. O., 2006; Connolly K. R., Thase M. E., 2011; Geddes J.R., Miklowitz D.J., 2013). It was believed that lamotrigine therapy may be associated with anomalies in palatability in the fetus, but the evidence obtained remains unconvincing.
Admission to the valprocom in the first trimester of pregnancy can cause a number of birth defects, from severe to lungs. If valproate is taken pregnant between the 17th and the 30th day after fertilization, the absolute risk of having a neural tube defect baby will be between 1% and 2% (especially lumbar meningomyelocyte). Studies have suggested the presence of a specific combination of congenital defects with prenatal effects of valproic acid (fetal valproic syndrome). These defects extend to the head and face, fingers, urogenital tract, mental retardation and physical development.
There is a correlation between the dose of the drug and small and large congenital malformations, which requires additional testing. Due to the risk of neural tube defects when taking the drug during critical periods of pregnancy, it is necessary to consult with regard to in-depth prenatal screening.
According to the FDA, valproic acid is contraindicated in pregnancy for the treatment of bipolar disorder, it is possible to prescribe this drug only in the case of ineffectiveness of other anticonvulsants.
Lamotrigine, unlike other mood stabilizers, is more effective for the prevention of depressive than manic episodes in BAD (Geddes J.R. et al., 2009). The efficacy of this drug in acute mania was slightly different from that of placebo (Frye M.A. et al., 2000).
Difficulties in the treatment of affective disorders in women are also in the fact that many additional factors in one way or another affect the pathogenesis of the disease. So, on the one hand, the effect of the disease on the menstrual cycle and reproductive function is on the one hand, and on the other hand it is drug treatment. In addition, physiological changes in the female body itself can cause aggravation of clinical manifestations of affective. In addition, it is necessary to consider the presence of comorbid conditions, especially polycystic ovary syndrome, which occurs in 4-19% of patients.
Unfortunately, there are currently no statistics on its prevalence among women with affective disorder, but researchers say their frequency is quite high in this category of people (Lobo et al., 1995). The accompanying syndrome is an extremely important factor as it can lead to hyperandrogenism (increased testosterone levels) and to anovulatory menstrual cycles and obesity, which significantly affects the general health of women. Polycystic ovary syndrome is more often observed in the treatment of salts of valproic acid, especially when this group of drugs was prescribed to girls under 20
years of age (Isojarvi et al., 1997). The pathogenetic mechanism of the development of this syndrome in women with epilepsy is associated with an increase in the level of luteinizing hormone. For those of reproductive age receiving estrogen contraceptives, certain recommendations for the dose adjustment of antiepileptic drugs are outlined, since their simultaneous administration leads to a decrease in the concentration of both drugs in plasma (Isojarvi, 1998).
Hormonal fluctuations occurring in premenopausal deepening the course of affective disorders, patients become more vulnerable, episodes of depression are more prolonged and severe, potentiating a decrease in estrogen levels during this period. In connection with this, it is recommended to combine treatment with substitution hormonal therapy.
Women are at high risk of recurrence of BAD during pregnancy, especially if the drug is stopped, as well as in the postpartum period. Balancing the risk of using drugs to prevent an affective episode requires active collaboration between health providers and the patient and his family (McKenna K. et al., 2005; McCormick U. et al., 2015). Most mood stabilizers have teratogenic risk. Lamotrigine is perhaps the exception, but this is not confirmed by well-controlled studies in humans. Atypical antipsychotic drugs, with the exception of lurazidone, are classified by the FDA when used in the pregnancy category C.
Conclusions. Analysis of patient groups for a therapeutic response showed that thiometabilizers showed the highest efficacy in the bipolar disorders M group (mania) for 4 weeks of therapy, and the bipolar disorders D group (depression) showed the least sensitivity to such therapy. And in 12 weeks the treatment with thimostabilizers there was a group ahead disorders E (eutymium), without a significant difference with the groups M and D. Additionally, all three groups showed the same risk of recurrence of the disease within 12 weeks after discontinuation of timostable stabilization: D-5 (12.5%) persons; M-4 (13.3%); E-6 (12.0%), as well as almost the same partial response to thiomostabilizers (12 weeks, 2 preparations): 3 (7.5%), 3 (10.0%) and 4 (8.0 %) person. It should be noted that in general, 12 people were monitored for a transition to a mixed state / mania within 12 weeks after initiation of therapy with antidepressants, of which 6 (12.5%) persons changed during the monitoring period in the D - group, and in 3 (13.3%) people of the M - group before the study before hospitalization. Instead, an increase in dysphoria or other symptoms in the use of antidepressants (4 patients, 10.0%), resistance to such therapy (3 patients, 7.5%) and an overdrive (< 1 week) response to antidepressant therapy (2 patients, 5, 0%) was observed only in the group -D. It should be noted that in women during the infiltration period, the frequency of rapid phase conversion was twice that of other age groups.
According to the FDA, valproic acid is contraindicated in pregnancy for the treatment of bipolar disorder, it is possible to prescribe this drug only in the case of ineffectiveness of other anticonvulsants.
Lamotrigine, unlike other mood stabilizers, is more effective for the prevention of depressive than manic episodes in ишзщдык disorders (Geddes J.R. et al., 2009). The efficacy of this drug in acute mania was slightly different from that of placebo (Frye M.A. et al., 2000).
Hormonal fluctuations occurring in premenopausal deepening the course of affective disorders, patients become more vulnerable, episodes of depression are more prolonged and severe, potentiating a decrease in estrogen levels during this period. In connection with this, it is recommended to combine treatment with substitution hormonal therapy.
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