Use of Lexapro during pregnancy and lactation
The effectiveness of escitalopram in the treatment of generalized anxiety disorder was demonstrated in 3 multicenter placebo-controlled studies lasting 8 weeks using doses of 10–20 mg / day. The study included patients aged 18 to 80 years with a diagnosis of GAD (in accordance with DSM-IV criteria). In all 3 studies, the improvement in escitalopram was significantly higher compared to placebo (assessment was based on the Hamilton Anxiety Scale, HAM-A).
There were too few patients with ethnic or age characteristics in these groups to evaluate their effect on the effect of therapy. The response to treatment was not dependent on the gender of the patients.
The effectiveness of escitalopram with prolonged (more than 8 weeks) treatment of GAD in controlled trials has not been systematically evaluated.
Panic Disorder.The efficacy of escitalopram was shown in a 10-week randomized double-blind study involving 351 patients. Patients after a 2-week introductory placebo period were randomized using escitalopram (n = 125), placebo (n = 114) or the active reference drug citalopram (n = 112).
In pregnancy, it is possible if the expected effect of therapy outweighs the potential risk to the fetus (adequate and strictly controlled studies of the safety of escitalopram in pregnant women have not been carried out).
The administration of escitalopram to pregnant rats in doses of 6, 12, 24 or 48 mg / kg / day, starting from the late stages of pregnancy and before weaning from the breast, led to a slight increase in the mortality of the offspring and growth retardation at a dose of 48 mg / kg / day (approximately 24 times the MRDR, when calculated in mg / m2). At the same dose, there was a slight toxicity to the maternal organism (clinical signs, reduced weight gain and food consumption). A dose of 12 mg / kg / day, at which no adverse effects were observed, is about 6 times higher than MRDC, when calculated in mg / m2.
According to the study of embryo / fetal development in rats, administration of escitalopram to pregnant rats orally at doses of 56, 112 or 150 mg / kg / day during organogenesis was accompanied by a decrease in fetal body weight and delayed ossification at 2 higher doses (approximately 56 times higher than mRDCH - 20 mg / day, when calculating in mg / m2). Maternal toxicity (clinical signs, reduced weight gain and food consumption), moderate at a dose of 56 mg / kg / day, was observed at all dose levels. The dose of 56 mg / kg / day, at which no influence on the development of the fetus was observed, was approximately 28 times higher than the MRDR, when calculated in mg / m2. No teratogenicity was detected at any of the tested doses (up to more than 75 times higher than MRDR, when calculated in mg / m2).
Newborns who were exposed to escitalopram and other SSRIs or serotonin and noradrenaline reuptake inhibitors at the end of the third trimester of the mother's pregnancy developed complications requiring prolongation of hospitalization, maintenance of breathing, and feeding through a tube. Such complications can occur immediately after delivery. Noted clinical symptoms included: respiratory distress, cyanosis, apnea, convulsions, unstable temperature, difficulty in feeding, vomiting, hypoglycemia, hypotension, hyperreflexia, tremor, nervous agitation, irritability, constant crying. These symptoms are associated with either the direct toxic effect of the SSRIs or serotonin and norepinephrine reuptake inhibitors, or may be manifestations of a withdrawal reaction in the newborn. In some cases, the clinical picture was similar to the development of serotonin syndrome.
If a patient takes escitalopram during the third trimester of pregnancy, the doctor should carefully evaluate the risk / benefit ratio, and consider the possibility of developing a cancellation reaction (a drug discontinuation syndrome) in the newborn. The doctor may decide on the gradual cessation of treatment with escitalopram in the third trimester.
The effect of escitalopram oxalate on childbirth and delivery in humans is not known.
Lactation. Breastfeeding women should stop either breastfeeding or taking escitalopram oxalate.
Drugs acting on the central nervous system. It is necessary to be careful at simultaneous reception with other drugs of the central action.
Alcohol. Although escitalopram does not potentiate the effects of alcohol (data from clinical studies), as is the case with other psychotropic drugs, the simultaneous use of escitalopram and alcohol is not recommended.
MAO inhibitors. Incompatible with MAO inhibitors (see "Contraindications" and "Precautions").
Means affecting blood clotting (NSAIDs, acetylsalicylic acid, warfarin, etc.). The release of serotonin from platelets plays an important role in hemostasis. Epidemiological studies (both a case-control study and a cohort study) demonstrated a link between the use of psychotropic drugs affecting serotonin reuptake and the frequency of bleeding from the upper GI tract. In two studies, the simultaneous use of NSAIDs, incl. acetylsalicylic acid, potentiated the risk of bleeding. Although these studies have focused on bleeding from the lower GI tract, there is reason to believe that bleeding and other localizations are possible, therefore, while taking escitalopram and agents that affect blood clotting, caution and monitoring of blood coagulation indicators are necessary.
Lithium. Lithium may enhance the serotonergic effect of escitalopram, therefore, when used together, care must be taken.
Sumatriptan. There are rare post-marketing messages about the development of weakness in patients, hyperreflexia, and impaired coordination of movements with the use of SSRIs and sumatriptan. In case the use of sumatriptan and SSRIs (such as fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically justified, appropriate monitoring of the patient is recommended.
Carbamazepine. Carbamazepine, inducing microsomal liver enzymes, can increase the clearance of escitalopram, which should be borne in mind when simultaneously prescribing these drugs.
Ritonavir. The combined use of a single dose of ritonavir (600 mg), which is both a substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) was not accompanied by a change in the pharmacokinetics of either ritonavir or escitalopram.
In vitro studies revealed no inhibitory effect of escitalopram on CYP3A4, CYP1A2, CYP2C9, CYP2C19 and CYP2E1. Based on these data, a slight effect on metabolism mediated by this group of cytochrome P450 enzymes in vivo is suggested.
CYP3A4 and CYP2C9 inhibitors. In vitro studies show that CYP3A4 and CYP2C9 are the main enzymes involved in escitalopram metabolism. However, co-administration of escitalopram (20 mg) and ritonavir (600 mg), a potent CYP3A4 inhibitor, did not have a significant effect on the pharmacokinetics of escitalopram. Since escitalopram is metabolized by different enzyme systems, inhibition of a single enzyme cannot significantly reduce clearance of escitalopram.
Drugs metabolized with CYP2D6 isoenzyme cytochrome P450. In vitro studies revealed no inhibitory effect of escitalopram on CYP2D6. In addition, the equilibrium levels of the racemate citalopram are not significantly different in the weak and strong CYP2D6 metabolizers. This indicates a low probability of a clinically significant effect of CYP2D6 inhibitors on escitalopram metabolism. However, limited in vivo data show a moderate CYP2D6 inhibitory effect of escitalopram: combined use of escitalopram (21 mg / day for 21 days) with tricyclic antidepressant desipramine (single dose of 50 mg), CYP2D6 substrate, resulted in a 40% increase in Cmax and a 100% increase AUC of desipramine. The clinical significance of this observation is unknown. However, caution is indicated when co-administering escitalopram and drugs metabolized by CYP2D6.
Metoprolol. A healthy volunteer intake of 20 mg / day of escitalopram for 21 days resulted in a 50% increase in Cmax and a 82% increase in AUC of metoprolol (a single dose of 100 mg). With increasing plasma level of metoprolol, a decrease in cardioselectivity was observed. Joint administration of escitalopram and metoprolol did not have a clinically significant effect on blood pressure and heart rate.
Electroconvulsive therapy. There are no clinical studies on the sharing of electroconvulsive therapy and escitalopram.
Since escitalopram is the active isomer of the racemate citalopram, these two drugs cannot be used simultaneously.
Modern ideas about the causes of depression
Bio-psycho-social model of depression.Modern science considers depression as a disease, the origin of which contributes to various reasons or factors - biological, psychological and social.
Depression Biology. The biological factors of depression include, first of all, specific disorders of neurochemical processes (the exchange of neurotransmitters, such as serotonin, norepinephrine, acetylcholine, etc.). These violations, in turn, may be hereditary.
Depression psychology. Scientific studies have identified the following psychological factors of depression:
- special style of thinking, so-called. negative thinking, which is characterized by fixing on the negative aspects of life and one’s own personality, a tendency to see the surrounding life and one’s future in a negative light
- specific style of communication in the family with a high level of criticism, increased conflict
- increased number of stressful life events in personal life (separation, divorce, alcoholism of loved ones, death of loved ones)
- social isolation with a small number of warm, trusting contacts that could serve as a source of emotional support
The social context of depression. The growth of depressions in modern civilization is associated with a high rate of life, an increased level of stress stress: high competitiveness of modern society, social instability - a high level of migration, difficult economic conditions, uncertainty about tomorrow. In modern society, a whole range of values is cultivated, condemning a person to constant dissatisfaction with himself - the cult of physical and personal excellence, the cult of strength, superiority over other people and personal well-being. It makes people hard to experience and hide their problems and failures, deprives them of emotional support and dooms them to loneliness.
Psychotherapy is not an alternative, but an important addition to the medical treatment of depression. Unlike drug treatment, psychotherapy involves a more active role of the patient in the treatment process. Psychotherapy helps patients develop the skills of emotional self-regulation and in the future more effectively cope with crisis situations without plunging into depression.
In the treatment of depression, three approaches have proven to be the most effective and scientifically based: psychodynamic psychotherapy, behavioral psychotherapy and cognitive psychotherapy.
According to psychodynamic therapy, the psychological basis of depression is internal unconscious conflicts. For example, the desire to be independent and the simultaneous desire to receive a large amount of support, help and care from other people. Another typical conflict is the presence of intense anger, resentment at others, combined with the need to be always kind, good, and to keep the disposition of loved ones. The sources of these conflicts lie in the patient's life history, which becomes the subject of analysis in psychodynamic therapy. In each individual case there may be a unique content of conflicting experiences, and therefore individual psychotherapeutic work is necessary. The goal of therapy is to recognize the conflict and help in its constructive resolution: to learn how to find a balance of independence and intimacy, to develop the ability to constructively express your feelings and to maintain relationships with people. Behavioral psychotherapy is aimed at resolving the current problems of the patient and the removal of behavioral symptoms: passivity, refusal of pleasure, monotonous lifestyle, isolation from others, inability to plan and engage in purposeful activity.
Cognitive psychotherapy is a synthesis of both of the above approaches and combines their advantages. It combines work with actual life difficulties and behavioral symptoms of depression and work with their internal psychological sources (deep ideas and beliefs). The main psychological mechanism of depression in cognitive psychotherapy is considered the so-called. negative thinking, which is expressed in the tendency of depressed patients to consider everything that happens to them in a negative light. Changing this way of thinking requires careful individual work, which is aimed at developing a more realistic and optimistic view of yourself, the world and the future.
Additional forms of depression psychotherapy are family counseling and group psychotherapy (but not any, but specifically aimed at helping depressed patients). Their involvement can provide significant assistance in treatment and rehabilitation.
What usually discourages seeking psychotherapy?
1. Low awareness of people about what psychotherapy.
2. Fear of the initiation of a stranger into personal, intimate experiences.
3. Skeptical attitude to the fact that the "talk" can give a tangible therapeutic effect.
4. The idea that you have to cope with psychological difficulties yourself, and turning to another person is a sign of weakness.
In modern society, psychotherapy is a recognized, effective method of assistance for various mental disorders. So, a course of cognitive psychotherapy significantly reduces the risk of recurrence of depression. Modern methods of psychotherapy are focused on short-term (10-30 sessions depending on the severity of the condition) effective help. All information that a psychotherapist receives in a session is strictly confidential and remains secret. A professional psychotherapist is specially prepared to work with difficult experiences and difficult life situations of other people, he is able to respect them and assist in coping with them. Every person in life has situations (such as illness, for example) that he cannot cope with on his own. The ability to ask for help and accept it is a sign of maturity and rationality, not weakness.
Help close people in overcoming depression
The support of loved ones, even when the patient does not express interest in her, is very important for overcoming depression.
In this regard, you can give the following advice to relatives of patients:
* Remember that depression is a disease in which sympathy is needed, but in no case should you dive into the disease with the patient, sharing his pessimism and despair. You must be able to maintain a certain emotional distance, all the time reminding yourself and the patient that depression is a passing emotional state.
* Studies have shown that depression is particularly unfavorable in those families where a lot of criticism is made to the patient. Try to make it clear to the patient that his condition is not his fault, but a misfortune, that he needs help and treatment.
* Try not to concentrate on the illness of a loved one and bring positive emotions into your life and family life. If possible, try to involve the patient in some useful activity, and not to remove him from the work.