Why do people with schizophrenia resist treatment?
Key Takeaways. Many people with schizophrenia suffer from anosognosia, which means they don't understand that they're sick—and, therefore, may not understand the need for treatment. Antipsychotic medication can cause side effects such as major weight gain, muscle spasms, and reduced sexual drive.
Why is clozapine used for treatment-resistant schizophrenia?
Clozapine is also indicated in patients with schizophrenia who show severe, untreatable adverse neurological reactions to other antipsychotics, including second-generation antipsychotics. Treatment with clozapine decreases overall mortality in schizophrenia, in part by reducing suicidality.Sep 4, 2020
What percent of schizophrenics are treatment-resistant?
Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high percentage of patients, approximately 30%, are classified as treatment-resistant (treatment-resistant schizophrenia; TRS).Apr 16, 2019
How is refractory schizophrenia treated?
For patients who do not respond to the first prescribed antipsychotic drug, current clinical practice is to switch to a second and a third drug, and eventually to clozapine, the only antipsychotic drug proven to be effective in treatment-refractory schizophrenia (TRS).
What causes anosognosia?
What Causes It? Experts think anosognosia results from damage to an area of the brain involved in self-reflection. Everyone, regardless of their health status, is constantly updating their mental image of themselves.Oct 20, 2020
Which drug is used for treatment-resistant schizophrenia?
Clozapine remains the first-line medication for treatment-refractory psychotic symptoms. In cases of partial response, the combination with SGAs such as sulpiride, amisulpride, aripiprazole, ziprasidone and risperidone is justified in order to supplement its antidopaminergic properties.
Can schizophrenia medication stop working?
Finally, some people with schizophrenia stop taking medication when they feel better. But that can backfire. Cutting back on or stopping the medication too soon can cause your symptoms to come back. Most people with schizophrenia take what doctors call a maintenance medication to keep things stable.Oct 26, 2021
What happens if antipsychotics don't work?
If you stop antipsychotics suddenly it can cause 'rebound psychosis'. This means that the symptoms of your illness return suddenly, and you may become unwell again. This is also known as 'relapse'.
What is it called when a patient does not respond to any medication for his disorder?
Specialty. Psychiatry. Treatment-resistant depression (TRD) is a term used in clinical psychiatry to describe a condition that affects people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time.
Which of the following antipsychotics is best for treating severe treatment-resistant schizophrenia?
Up to 30% of people with schizophrenia do not respond to two (or more) trials of dopaminergic antipsychotics. They are said to have treatment-resistant schizophrenia (TRS). Clozapine is still the only effective treatment for TRS, although it is underused in clinical practice.Nov 7, 2016
What do you mean by refractory schizophrenia?
The most recent algorithm, the Schizophrenia Algorithm of the International Psychopharmacology Algorithm Project (IPAP) (www.ipap.org) defines that a patient is considered to be refractory if he or she failed to respond to two trials of 4 to 6 weeks of duration of monotherapy with two different SGA (or two trials with ...
What is refractory mental illness?
The Refractory Mood Disorders Program, part of the Center of Excellence on Mood Disorders, leads research in the development of innovative treatment options for refractory mood disorders. Refractory, also known as treatment-resistant, describes conditions that do not respond to at least two different medications.
Why is schizophrenia not responding to treatment?
8 A large number of patients have schizophrenia that does not respond because pharmacological, psychological, and psychosocial treatments are inadequate.
How long does chronicity last in schizophrenia?
In contrast with treatment-resistant schizophrenia, chronicity is associated with a favorable response to drug treatment, in which schizophrenic features are largely under control for 6 months or longer or there is partial recovery to the premorbid level of functioning. 4,5.
How long does it take to take chlorpromazine?
Although there are no universally accepted criteria, a common convention is that adequate drug treatment requires a duration of 4 to 10 weeks, a dosage equivalent to 1000 mg/d of chlorpromazine, and trials of 2 to 3 different classes of antipsychotic drugs. 6 Table 1 presents suggested doses of atypical antipsychotics based on recent comparisons of efficacy. 7
What is cognitive behavioral therapy?
Among various models (including personal therapy, psychodynamic psychotherapy, and family treatment), cognitive-behavioral therapy (CBT) is considered most effective. 34,35 The primary aim of CBT is to improve understanding and insight of schizophrenia and enhance coping mechanisms for psychotic and depressive symptoms.
How long does it take to treat schizophrenia with clozapine?
Typical antipsychotics can be used for 4 to 6 weeks to screen for treatment-resistant schizophrenia, after which treatment with clozapine may be considered.
When should clozapine be used?
Clozapine should be used only when it is confirmed that patients have treatment-resistant schizophrenia and their condition fails to respond to atypical antipsychotics or typical antipsychotics. The same rule applies in identifying clozapine-resistant schizophrenia.
How many antipsychotics should be tried for schizophrenia?
As shown in the Figure, at least 2 antipsychotic drugs should be tried at adequate dosage and for an adequate period, and various factors that interfere with adherence should be ruled out before making a diagnosis of treatment-resistant schizophrenia.
What is the best treatment for TRS?
Treatment Alternatives for TRS. Despite recent controversy, clozapine for TRS remains the most established treatment option. However, if an individual is unable to tolerate or is refusing clozapine, high-dose monotherapy with an alternative antipsychotic can be considered. High-dose olanzapine, at a dosage of 30-40 mg/d, ...
Can psychopharmacology be copied?
Psychopharmacology. This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.
Is clozapine good for TRS?
Conclusion. For individuals with TRS, clozapine should be considered. Some evidence supports high-dose olanzapine for TRS. Due to the varied symptom presentation of TRS, individual symptoms should be specifically addressed rather than utilizing a "one size fits all" approach.
Does clozapine reduce dopamine?
Clozapine is unique from other antipsychotics in that it may function as an NMDA receptor modulator by increasing glycine levels and thus alleviating NMDA receptor hypofunction and consequently reducing excess dopamine signaling in the mesolimbic pathway. 13.
Is topiramate good for psychopathology?
Topiramate was also found to be effective for positive and negative symptoms, as well as general psychopathology, but is not recommended due to a higher discontinuation rate. With lamotrigine, after removal of 2 outliers, there was no significant difference between lamotrigine augmentation and clozapine monotherapy. 16. ...
Is Clozapine good for schizophrenia?
Glutamate Hypothesis of Schizophrenia. An explanation for clozapine’s superior efficacy may rest with the glutama te hypothesis of schizophrenia. In individuals with schizophrenia, there is an increase in striatal presynaptic dopamine synthesis capacity.
Does memantine affect NMDA?
Minocycline and memantine modulate the NMDA glutamate receptor and perhaps moderate glutamate-mediated excitotoxicity. A memantine augmentation study for clozapine-refractory patients showed memantine to be effective for negative symptoms, with mixed findings on cognitive symptoms. 17 A meta-analysis of minocycline augmentation in schizophrenia ...
What is the second component of symptomatic assessment?
The second component of symptomatic assessment is the determination of response to treatment relative to a baseline. Ideally, this should be performed prospectively for two treatment episodes with different antipsychotic drugs. While this will not always be practical, it is recommended that there be at least one prospective evaluation of treatment efficacy. If this is not possible, then this should be clearly specified and a retrospective assessment of response to treatment obtained as a minimum. A change of 20% is the minimum that can be routinely detected clinically ( 32 ). Therefore, a reduction of less than 20% will correspond to a clinically insignificant reduction in symptoms. It could be argued that larger reductions may still not be clinically meaningful. However, given that an improvement of ≥20% has been used to identify treatment responders ( 33 ), requiring a reduction of <20% ensures that the treatment-resistant group does not overlap with treatment responders. Therefore, it is recommended that at the end of the prospective evaluation, the absolute symptom severity rating criteria described above should still be met, and that symptom reduction should be <20% both for the total rating and the specific domain of interest before such a patient is included in a prospective treatment trial of treatment-resistant schizophrenia. In the event that a patient shows an improvement of ≥20% during the prospective observation period, then the patient should be re-evaluated and, if absolute criteria for treatment-resistance are still met, be observed for another prospective evaluation period. Only patients who during the prospective observation improve by <20% and still fulfill absolute severity thresholds for treatment resistance should be categorized as having treatment-resistant illness and included in prospective studies. In contrast, precise quantitative assessment is unlikely to be feasible for retrospective evaluation (which is exactly why we recommend prospective evaluation of treatment resistance). Therefore, for past treatment episodes, we recommend that patients should be rated as less than “minimally improved” on the overall change in the Clinical Global Impression–Schizophrenia Scale ( 34 ). It is recommended that multiple sources of information, including patient and caregiver reports, case notes, and staff report, be used to evaluate past response. Nevertheless, because measurement error is likely to be larger in the retrospective evaluation of response to past treatment, in order to be conservative, it is recommended that where there is missing information or doubt, investigators err on the side of caution and exclude subjects or prospectively evaluate nonresponse in at least this subgroup. A further important requirement is that investigators ensure that rating scales are adjusted to a baseline of zero. For example, a score change from 90 to 60 in the 30-item PANSS, in which each item is scored 1–7, represents a 50.0% reduction rather than 33.3%. Using a nonzero score for absent symptoms with the PANSS will lead to underestimation of treatment effects when percentage change in symptoms is calculated ( 35 ).
What is the failure of at least two adequate treatment episodes with different antipsychotic drugs?
Failure of at least two adequate treatment episodes with different antipsychotic drugs, each meeting the above criteria, is required to establish treatment resistance. In some clinical guidelines it is recommended that these trials include different types of antipsychotics (such as first- and second-generation drugs) ( Table 1 ). However, given the overlap in side effects, efficacy, and receptor profiles among currently available non-clozapine antipsychotics, the consensus was that the current data do not delineate distinct categories of non-clozapine antipsychotics ( 11, 55 ). There was some disagreement about this conclusion among the working group members, as olanzapine, risperidone, and amisulpride show consistent, although small, advantages in meta-analyses of efficacy ( 56 ). However, consensus was reached that, when considering this from a practical perspective as well, specifying particular drugs would limit generalizability, not least because a given drug may not be readily available in some settings (for example, amisulpride in the United States). In view of this, a requirement to use particular categories or drugs (apart from clozapine) is not currently recommended. Of course, particular drugs may be stipulated in a given study when there is a specific reason to focus on patients who have not responded to a certain drug or group of drugs. In practice, many patients will have tried a large number of different drugs ( 16 ). In view of this, the total number of failed adequate antipsychotic treatment trials, the drugs, and their dosage and route of administration should be ascertained and reported where possible. As mentioned above, a trial with a long-acting injectable antipsychotic would be optimal to establish treatment resistance not confounded by treatment nonadherence.
What is a comparator group in a cross sectional study?
Cross-sectional and mechanistic studies will often require a comparator group of participants who have shown a good response to treatment. For consistency, the same clinical rating scales should be used to identify this group as those used to identify the treatment-resistant group. In addition, the criteria need to ensure that there is a clear distinction between groups. This precondition requires that the criteria make allowance for measurement error and have a clear separation of thresholds in order to avoid the inclusion of participants rated in a borderline zone who are potentially eligible for both groups, depending on the rater or the day that they are rated. Thus, it is recommended that for an absolute symptom threshold, responders show no more than mild symptom severity across the symptom items in the domain (s) of interest, and that they have shown this over at least 12 weeks. Where possible, it is recommended that response be ascertained prospectively over at least 6 weeks and defined as at least a 20% improvement in symptom scores for the domain of interest as well as meeting the absolute thresholds. Furthermore, there may be circumstances—for example, studies in first-episode patients—where this threshold may be of insufficient stringency. In these circumstances, investigators may choose even more rigorous stability criteria to define adequate treatment response, such as having achieved remission, consisting of no more than mild positive and negative symptoms for ≥6 months ( 8) or no symptoms at all. In addition to the symptom severity threshold, current functional impairment should not be more than mild (e.g., a score >60 on the SOFAS) in all circumstances. Table 3 presents a summary of the criteria.
What are the criteria for treatment resistance?
First, the criteria must encompass a core definition of treatment resistance that captures the worldwide understanding of the concept. Second, the criteria must be applicable across a range of study designs, from longitudinal clinical trials to experimental medicine studies to cross-sectional mechanistic investigations. Third, the criteria must identify a group of patients who are clearly distinct from those whose illness is not treatment resistant. Finally, the criteria must be practical, so that they can be used in a wide range of settings but still be rigorous.
What is schizophrenia?
Schizophrenia is a severe mental disorder characterized by positive, negative, and cognitive symptoms ( 1 ). The treatment of schizophrenia was revolutionized by the introduction of chlorpromazine in the 1950s ( 2 ).
Why is nonadherence important in schizophrenia?
Because of difficulties with adhering to dosing schedules, lack of illness insight, side effect burden, cognitive impairment, and other factors , nonadherence is a significant problem in the treatment of schizophrenia and is often underrecognized ( 78 – 81 ). Nonadherence may be the single largest source of unrecognized error in studies of treatment resistance ( 78 ). Consequently, it is important to make strenuous efforts to determine adherence and to apply criteria to exclude poorly adherent subjects, who can represent false positive “pseudo-resistant” cases. While 100% adherence is rare even in clinical trial settings ( 82, 83 ), it is necessary to be close to this figure; otherwise, the study will be of nonadherence rather than of treatment resistance.
Is Clozapine a treatment resistant drug?
For clarity, and because of the specific role of clozapine in the treatment of resistant schizophrenia ( 58 – 62 ), failure to respond to clozapine is to be used as a subspecifier of treatment-resistant illness—“clozapine-resistant schizophrenia.” In addition to using the midpoint of the dosage range as a minimum requirement for an adequate trial, and the adherence requirements described below (section 5.5), it is recommended that trough serum levels of clozapine be measured on at least two occasions separated by at least 1 week at a stable dosage of clozapine. This is important not only to establish adherence but also because of the link between serum levels of clozapine and response ( 63 – 67 ). Clozapine levels ≥350 ng/mL ( 68) constitute an optimum threshold requirement for establishing nonresponse to clozapine treatment. It is strongly recommended that serum levels be used, not least because of the major effect of smoking and gender on clozapine’s pharmacokinetics, but when obtaining blood samples is not feasible, a minimum dosage of 500 mg/day is recommended, unless tolerability issues restrict the dosage range. This dosage is in the middle of the approved range for clozapine, and it was only at dosages over 400 mg/day that clozapine proved superior to other antipsychotics in a meta-analysis of head-to-head comparisons ( 69 ).
