Quetiapine (seroquel) and biopsychosocial approach in schizophrenia
Schizophrenia as a biopsychosocial phenomenon requires long-term combined drug and psychosocial treatment. With adequate care, the clinical and functional outcome of schizophrenia is no less favorable than in a number of diseases requiring conservative or surgical treatment (arthroplasty, coronary bypass) . Psychopharmacotherapy is an integral part of the biopsychosocial treatment of a patient with schizophrenia. The clinical efficacy (in daily practice) of typical neuroleptics (TN) and atypical antipsychotics (AA) is composed of interrelated safety indicators (individual tolerability), satisfaction with treatment, compliance of patients. A scientifically justified choice of VT or AA is determined by the best risk ratio (early and delayed adverse effects) / benefit (clinical effect) of therapy and the preferences of the patient and his loved ones. The choice of the drug is dominated by a precautionary principle: minimizing the risk of unwanted actions, taking into account the patient’s suspected sensitivity and in the context of his professional and daily activities (for example, small finger tremor is a tragedy for a musician). The effect of a TH or AA is predicted by the doctor, based on the experience of treating the patient or his blood relatives (incidentally, their awareness of the details of treatment and the need for information is revealed). The selling price of AA (seroquel) is two orders of magnitude higher than the TN in terms of the daily dose, but pharmacoeconomic studies indicate that the former has an illusory-objective value in formulating the form and choosing a doctor. After all, the cost of antibiotics and immunosuppressants is not less, but priority in financing health care. The resource-saving potential of AA manifests itself fully in their rational choice and application . The position of the national clinical guidelines  is consistent with the recommendations for the treatment of schizophrenia in a number of European countries: AA is shown in the absence of the expected (acceptable for the doctor, patient, his loved ones) clinical response and / or high risk or development of undetectable undesirable effects of TN in a minimal therapeutic dose , causing significant distress in the patient and reducing his social functioning and quality of life. This step-by-step approach is a proven cost-effective strategy in the face of a scarcity of medical resources . The criterion for deciding on the choice of AA was the ethical principle of justice – a non-discriminatory, reasonable, differentiated distribution of limited medical resources for the treatment of certain groups of patients with limited therapeutic options in comparison with the population of schizophrenia. The success of the treatment is facilitated by the productive union of the patient, his relatives with the doctor-adviser (members of the multidisciplinary team), joint planning of treatment for the consistent resolution of the patient’s personally significant problems (from getting rid of blasphemous “voices” before returning to the profession), forming the responsibility of the patient and his relatives for the result of treatment. The strategic goal of biopsychosocial treatment is unchanged: improving the clinical and functional outcomes of schizophrenia, alleviating its multiple burdens for the patient and his loved ones, psychiatric and general medical services, society as a whole. However, the tasks of therapy change in connection with the phase of the disorder [6, 9, 25, 26].
Acute (stop) treatment of patients in the first episode, relapse or exacerbation of schizophrenia is aimed at the early stabilization of psychotic disorders; identification of individual psychosocial triggers of an acute condition; prevention of prolonged social disadaptation of the patient. The purpose of treatment of paroxysmal forms: the achievement of the deepest remission, continuous forms – compensation of psychotic disorders within the framework of therapeutic remission. Explanatory work with the patient (the meaning of treatment to alleviate the most disturbing symptoms, an individual prognosis, preferably in an optimistic manner) strengthens the setting for treatment during the “latent” period of the drug. Education of close, active participants in the process of therapy is important in the formation of a protective and protective environment. It is important to “imprints” (imprinting) positive events in acute treatment, and negative impressions result in the rejection of subsequent treatment, distress. When hospitalization should be avoided whenever possible physically constraining the patient, prolonged isolation in the monitoring room. Disturbance of patients, lack of exercise and lack of employment, roughness, internal conflicts of personnel are risk factors for the patient’s aggression in the hospital department even against the background of “good medicine”. It is preferable to take drugs inside and only if necessary to resort to parenteral administration. However, some physicians are inclined to start acute treatment with intramuscular forms of VT, or, more rarely, AA, unreasonably believing that this method is more effective .
However, no more than 10% of patients require parenteral administration of the drug in connection with the rejection of tableted forms. A number of patients perceive injections as a repressive measure, evidence of a particular danger of their condition. In addition, injections are painful (especially for patients with a reduced pain threshold), are costly and fraught with complications (respiratory depression, infiltrates).
Seroquel in connection with its safety can be appointed until the results of laboratory tests are obtained; in urgent cases, when the patient resists examination (but not taking the medicine) – until a complete medical examination. Probably a trial 48-hour treatment with trial doses of seroquel (50-100 mg) to identify the individual sensitivity of the patient with an assessment of his subjective reaction . Seroquel less often than TN, causes dysphoria, emotional indifference. Such an unpleasant and memorable early symptomatology, which outstrips the therapeutic effect, often leads to the rejection of further treatment. Hypotension (it is important to prevent the patient, especially the elderly, not to stand up sharply, avoid dehydration, especially in summer) and dry mouth (good rinse, chewing gum without sugar) are usually reduced as they adapt to seroquel, like most of the early “general toxic” actions of neuroleptics [ 1].
In psychogerontological practice, the risk of orthostatic hypotension (to prevent abrupt rising from bed) and dizziness
(with possible falls), tachycardia in the initial stage of treatment (the initial dose of seroquel should not be more than 25 mg, the slower the dose, the better the drug is tolerated). The risk of ventricular tachyarrhythmia in the treatment with seroquel (10%) corresponds to that in the treatment with tableted haloperidol and 1.5 times less than when treated with risperidone . In acute treatment, the speed of the drug is important. Olanzapine inside (including the resorption form) requires 5-8 hours for its concentration in the blood plasma to peak, oral haloperidol – 4 hours, risperidone and seroquel – 2 hours. It is possible to increase the dose of quetiapine to 800-1000 mg for a 3- 5 days (200 mg / day) with asymmetric two-time appointment of most of the drug at night, if necessary in combination with high-potency tranquilizers (lorazepam, phenazepam). The non-specific calming effect of seroquel without hypersedition (the need for tranquilizers is reduced) is useful for prompt, within 5-7 days, arresting the agitation and hostility of patients , is positively perceived by patients, does not interfere with detailed somatoneurological evaluation and early psychosocial interventions. While the risk / benefit ratio of quetiapine is above the recommended threshold, little is known about it, but within the therapeutic range, with the selection of seroquel (up to 750 mg / day), psychotic anxiety decreases within a week .
Gradual build-up of doses (up to 400 mg / day for 5 days) is shown elderly and with liver diseases. Doses of seroquel 450 mg / day, approximately equivalent to 8 mg of haloperidol, are usually sufficient for patients in the first episode of schizophrenia. The efficacy (in RCTs) of acute treatment with seroquel (400-800 mg / day), olanzapine (10-20 mg / day) and risperidone (4-8 mg / day) is similar . The antipsychotic effect of seroquel is most pronounced to the 8th-12th week in 50-85% of patients . Seroquel monotherapy avoids the risk of pharmacokinetic interactions and a complex treatment regimen for the patient and medical staff. A smaller need for anticholinergic correctors (cyclodole), exacerbating and prolonging psychosis, having the potential of dependence and aggravating cognitive frustration of schizophrenia, contributes to the optimization of therapy in the choice of seroquel. The widespread combination of seroquel with VT and other AAs in everyday practice (up to 40%) is associated with the doctor’s impatience , not taking into account the risk of treatment at its rise in price, blurring the clinical picture . In acute treatment, patients prefer seroquel to a number of other AA and TN , especially those who avoid taking medication because of increased sensitivity to neurological and metabolic (obesity, hyperprolactinemia) side effects, such as in the first episode of schizophrenia  . Thus, weight gain causes no less distress than acute neurological disorders, especially in young girls (at risk), which is important when choosing an antipsychotic to avoid a later break even of successful clinical therapy. The risk of weight gain (in 25% of patients, usually not more than 4 kg for the first 12 weeks with subsequent access to the plateau for a one-year treatment) in seroquel is lower than in a number of AA .
Against the background of seroquel, the initially increased weight may even decrease. In everyday practice, however, the majority of patients are treated with a combination of drugs, including a high risk of weight gain (for example, “classical” tricyclic antidepressants, lithium), and the beneficial effect of seroquel against polypharmacy may be lost. Therefore, it is important to teach the patient the skills of a healthy lifestyle (exercise, low-calorie diet). Ineffectiveness of treatment is noted in the absence of positive dynamics in the clinical and functional areas of assessment, including the subjective – the patient himself, within 3-8 weeks after reaching the therapeutic dose of seroquel; with a partial response, treatment should be continued for another 4-10 weeks.
With ineffective treatment, a reassessment of the patient’s mental and physical condition is necessary (revealing hidden organic inferiority, substance abuse, affective disorders, compliance problems, chronic psychosocial distress, increased emotional experience in the family). It is possible to increase the dose of quetiapine after 6-8 weeks of treatment, but ultrahigh doses should be avoided. The practice of premature replacement of quetiapine with another drug or polyneurosis leads to the fact that the cause for improvement of the patient’s condition and undesirable actions remains unclear for the doctor. The transition to seroquel is logical in the case of uncontrolled undesirable phenomena of VT (for example, acute extrapyramidal disorders) or other AA, with the exception of clozapine (for example, obesity). A method of cross-titration that minimizes the risk of symptoms of “ricochet”, sometimes interpreted by a physician, as undesirable actions of a new treatment is desirable (Table 1).
The orderly behavior of the effect of seroquel with the “distancing” of the personality from the remaining psychotic experiences makes it possible to start individual and then group psychosocial interventions (training in management of the disease and its treatment) at the early stages of hospital treatment, continuing at discharge. Therapy includes a number of components:
• detection and prevention of relapse factors, active control of the “early” symptoms of worsening;
• urgent treatment when they are identified by a joint crisis plan worked out jointly with the doctor and close (management of distress, intensification of observation and treatment, strengthening of informal support);
• training in effective coping skills with symptoms and family (family) distress, drawing on the positive experience of group members and behavioral techniques, learning to solve common problems and social skills in the organization of treatment (seeking help, alliance with loved ones and professionals);
• Individual or group family therapy for emotional support, learning to cope with the illness of a loved one through understanding the active role in treatment, reducing excessive emotions as triggers of relapse, and prevention of distress.
As the patient’s condition is stabilized, it is necessary to switch to a treatment that is effective for acute treatment with a drug (seroquel) to prevent early relapses and exacerbations, to strengthen and consolidate the success of therapy. As remission deepens, the patient increasingly acts as a subject of treatment on the principles of partnership. The psychiatrist (social worker, clinical psychologist) focuses on the patient’s problems outside the protected environment of the hospital (day hospital): limits unrealistic expectations and requirements for the functioning of the patient in his family. It is necessary to balance the stimulation of patient responsibility for the result of treatment and the provision of emotional and social protection. It is important to save the patient and his loved ones from the fatalistic expectation of a return of psychosis, orient them to a healthy lifestyle. The management of the patient is focused on evaluating, supporting, explaining, strengthening the sense of reality, changes in his behavior. Relief of psychotic symptoms in the treatment of seroquel allows you to indirectly master (restore) social skills. Group psychosocial therapy is used to develop skills for management of illness and treatment, it is useful to involve the patient and his relatives in the activities of the self-help society in the community (an important part of the treatment plan). Improvement of symptoms outstrips the improvement of social and labor functioning. The nature and extent of disability is a more relevant and real measure of the outcome of schizophrenia treatment than a change in the clinical picture (“target syndrome”). A clear sign of a patient’s social recovery is a return to an occupation appropriate to age. When persistent symptoms need to strengthen psychosocial treatment (cognitive-behavioral therapy).
Pharmaco-dependent remissions with “blurred” symptoms, which are actualized with the abolition or reduction of doses of TN or AA in more than 60% of patients with schizophrenia, determine the continuation of treatment with total (unchanged) doses of quetiapine by the majority of community-acquired patients. The treatment regimen should correspond to the daily functioning of the patient, and it should be simplified, which will improve compliance and facilitate its monitoring by trained relatives. It is advisable to “asymmetric” the reception of most of the seroquel in the evening, since the drug in medium doses is prescribed twice a day, but the clinical effect in patients receiving the drug once a day is similar . When revealing the early symptoms of relapse (the topic of psychoobrazovaniya) may increase the dose of seroquel by 100-200 mg with a temporary attachment of tranquilizers.
Clinical problems in the development of remission. Experiencing a state of “awakening”, that is, a pronounced and rapid clinical improvement in the treatment with seroquel, patients reveal a wide range of reactions (alienation of the disease, reactive depression), disrupt the treatment regimen and therefore require intensive emotional support, since their “I” did not have time to adapt to new ones social problems, and the family of the patient is not always able to perceive with understanding the new role of the patient, more habitual in the inhibited state. The condition is transient, it is possible to appoint tranquilizers for up to a week. Negative disorders, their severity (buildup) is difficult to detect in an acute period. It is necessary to distinguish caused, for example, TH, akinesia, as well as depressive anhedonia, paranoid asociality, impoverishment of speech in thinking disorders from primary negative symptoms. It should be explained to the close nature of the patient’s changes (not “laziness”), cautiously prepare them for the idea that patients may not return to a painful condition, and for improvement, not only medication but psycho-social effects are required. The negative disorders that come to the forefront are the basis for choosing seroquel, if it has not already been assigned, keeping in mind its possible antidecitant and cognitive-impairing effects (at least, it does not exacerbate their undesirable actions), but it’s worthwhile to set up the family not to rely on the fast ” miracle “(to determine the effectiveness of treatment requires at least six months) and call for active cooperation in the case of resocialization of the patient. After all, the “defect” of the patient in many respects is his personal compensatory reaction to the neglect of others, and “learned helplessness” is a consequence of understated requirements in the hospital and community settings. Therefore, the heaviest patients should be sent as soon as possible to the rehabilitation department to develop (restore) social skills, in more light cases – in the day hospital for the continuation of the rehabilitation program or home to the care of relatives with compulsory communication with social services. An unpublished extract from the hospital is fraught with an increase in the burden of schizophrenia for the family and the rapid deterioration of the patient’s condition. Post-schizophrenic depression is possible in 50% of patients, although in the majority (up to 60-80%) of cases active treatment of TN or AA (seroquel) and intensive psychological support in the acute period contribute to resolving depression within the psychosis. In case of depression, the doctor will have to eliminate the previously unrecognized organic disease and schizoaffective disorder, the distress after the previous psychosis, the prolongation of a new episode, treat any concomitant medical illnesses, exclude substance misuse and neurological undesirable actions (akinesia, akathisia can not be ruled out in the treatment of any TN or AA) , to reveal the psychotraumatic situation that is persisting or brought by the illness in the family or at work. A necessary condition for treatment is the information of relatives about the risk of suicidal tendencies in the patient, creating an atmosphere of reasonably weighed optimism. It can be assumed that the harmonious effect of quetiapine on all components of an acute attack will allow for a deeper remission (including a decrease in the frequency of post-schizophrenic depression). With depression in the background of seroquel, treatment with antidepressants of the new generation is shown for at least 6 months [9, 26]. With the difficulty of distinguishing between depressive symptoms and negative, a trial course of antidepressant therapy is shown. The appointment of antidepressants without seroquel can exacerbate psychosis.
Non-compliance with treatment regimens. Good tolerance of seroquel does not guarantee continuation of treatment without systematic psychosocial work with the patient and his relatives, since the main causes of long-term compliance problems are the internal picture of the disease (the patient does not need treatment, he is actively opposed to medicines), an unsatisfactory therapeutic alliance with a doctor , disinterest of the family in the results of treatment. At least 50% of patients lose their relationship with HDPE in the first months after discharge from the hospital. A number of patients, stopping treatment on their own, note that they feel good after 3-4 weeks. It is necessary to take into account the incompletely formed reaction to the acute period, the patient’s vulnerability to psychosocial stresses, possible undesirable actions of therapy, to explain to the patient and his family that the risk of deterioration is high and he is delayed in time, and the path to recovery is long, but “the path will master the going.”
Antiretpressive (maintenance) therapy reduces the risk of recurrences (exacerbations) of schizophrenia and, apparently, slows down the rate of its progression. Treatment is necessary as long as the underlying pathology persists, and does not imply that the risk of relapse is reduced after discontinuation of medication and that in the future it will not need its renewal. Secondary prevention is more important than the risk of unwanted effects of drugs, since most of them are reversible, and the consequences of relapse can be fatal. Adequate pharmacotherapy (“the right medicine for the right patient”) allows to improve, consolidate the achieved therapeutic results with the least risk of undesirable actions. In connection with the unclear prediction of the cessation of activity of the painful process, supportive treatment is indicated to all patients. For patients who have undergone the first episode and are fully remorted within a year, gradual withdrawal of seroquel treatment within one to two years is possible [6, 9, 26]. At least 5 years to be treated in the absence of psychotic symptoms to patients with repeated attacks. Preventive treatment during life is shown by a third of chronic patients, especially dangerous for themselves and others in an acute period (or if repeated psychoses differed in duration and did not respond well to therapy). For many patients, a psychiatrist becomes a general practitioner. He should pay more attention to the state of physical health and well-being of patients, dynamically controlling the possible undesirable effects of prolonged therapy. In this regard, low risk of unwanted effects of seroquel with long-term use  is important, for example, tardive dyskinesia, a scourge of maintenance therapy for TH or obesity in the treatment of a number of AA. The choice of seroquel is indicated by the stabilized symptomatically ill, but experiencing these side effects that are not otherwise corrected. Reduction of seroquel dose due to good tolerability and low risk of dose-dependent adverse effects is not useful in patients with pharmacologically dependent remission; in others, it is possible (if the risk / benefit ratio is re-evaluated) not earlier than 6-12 months of stable relief of symptoms of paroxysmal schizophrenia, control. The minimum therapeutic dose of seroquel is determined by physicians after trial and error. With insufficient doses of quetiapine, relapses (exacerbations) may be delayed for several months, and therefore serve as an unreliable indicator. Good tolerability of seroquel in combination with its high antiresidivnoy efficiency contributes to the satisfaction of patients with long-term treatment [11, 14, 17, 21, 24]. However, discontinuation of AA therapy (ziprasidone, quetiapine, olanzapine, risperidone) in chronic patients reaches 75% within 18 months, and is only slightly determined by drug intolerance . Screenings in seroquel treatment are 80% within three years , which emphasizes the danger of neglecting psychosocial work to strengthen and control long-term compliance of patients.
So, in the first months of treatment with seroquel, the main efforts are aimed at reducing psychotic symptoms with minimal risk of unwanted effects of therapy. After 3-12 months, the emphasis is shifted to preventing relapses (exacerbations), maintaining and monitoring compliance by the patient, reducing the risk of medical complications of therapy, social and labor engagement and meeting the changing needs of the patient and his family. After a year, the therapy focuses on ensuring an independent and happy life for most patients, regardless of the “length of service” of their disorder.
The symptomatic effect, social functioning and quality of life of a patient with schizophrenia when treated with seroquel will be higher with coordinated interprofessional and interagency interventions (Table 2).
Seroquel opens the locks of early rehabilitation (due to the ordering action); contributes to the establishment of a stable full-fledged remission (antipsychotic and antiresidivnye effects), as the basis of social recovery . A “patient-friendly” seroquel with a close to optimal ratio of risk / benefit therapy is the first choice drug at successive stages of systematic biopsychosocial treatment of schizophrenia.
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