Treatment-resistant schizophrenia (TRS) is a condition that affects about a third of people with schizophrenia, who do not respond well to standard antipsychotic medications. TRS is a major challenge for the management and prognosis of schizophrenia, as it is associated with more severe symptoms, poorer quality of life, higher risk of suicide, and higher health care costs. In this essay, I will discuss the definition, signs and symptoms, causes, diagnosis, treatment, complications, and therapies of TRS.
What is Treatment-Resistant Schizophrenia?
TRS is usually defined as a failure to achieve adequate symptom relief after trying at least two antipsychotic drugs of sufficient dose and duration, as prescribed by a doctor. However, there is no consensus on the exact criteria or time frame for diagnosing TRS, and different studies may use different definitions. Some factors that may influence the diagnosis of TRS include the type, dose, and duration of antipsychotic drugs, the severity and duration of symptoms, the adherence to treatment, the presence of comorbidities, and the response criteria.
What are the Main Signs and Symptoms?
The signs and symptoms of TRS are similar to those of schizophrenia, but they are more persistent and disabling. They include positive symptoms, such as hallucinations, delusions, and disorganized speech and behavior; negative symptoms, such as apathy, anhedonia, and social withdrawal; and cognitive symptoms, such as impaired attention, memory, and executive functions. TRS may also cause affective symptoms, such as depression, anxiety, and mood swings; and somatic symptoms, such as weight gain, metabolic syndrome, and movement disorders.
How Does Treatment-Resistant Schizophrenia Develop?
The causes of TRS are not fully understood, but they may involve multiple biological, psychological, and environmental factors. Some possible causes of TRS include:
- Neurotransmitter dysfunction: TRS may result from an imbalance or dysfunction of various neurotransmitters in the brain, such as dopamine, glutamate, serotonin, and gamma-aminobutyric acid (GABA). These neurotransmitters are involved in regulating mood, cognition, perception, and behavior, and they may be affected by genetic variations, epigenetic modifications, or environmental influences.
- Neuroinflammation: TRS may be linked to chronic inflammation in the brain and nervous system, which may be triggered by infections, stress, trauma, or autoimmune disorders. Neuroinflammation may damage the brain cells and circuits, and alter the immune system and the blood-brain barrier, leading to neurodegeneration and neurotoxicity.
- Schizophrenia subtype: TRS may represent a distinct subtype of schizophrenia, with a different disease course, prognosis, and response to treatment. Some researchers have proposed that TRS may be classified into two subtypes: primary TRS, which is present from the onset of schizophrenia and is more resistant to treatment; and secondary TRS, which develops over time and is more responsive to treatment.
Diagnosing Treatment-Resistant Schizophrenia
The diagnosis of TRS is based on the clinical judgment of a psychiatrist, who will evaluate the patient’s history, symptoms, response to treatment, and other relevant factors. The psychiatrist may use various tools and scales to assess the severity and impact of the symptoms, such as the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI), and the Global Assessment of Functioning (GAF). The psychiatrist may also order some tests to rule out other possible causes of the symptoms, such as medical conditions, substance abuse, or medication side effects.
Treatment-Resistant Schizophrenia NICE Guidelines
Treatment-resistant schizophrenia (TRS) is a condition in which people with schizophrenia do not respond adequately to at least two different antipsychotic drugs. The NICE (National Institute for Health Care Excellence, UK) guidelines for managing TRS are as follows:
- Offer clozapine to adults with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. At least one of the drugs should be a non-clozapine second-generation antipsychotic.
- Before starting clozapine, offer the person a full discussion of the benefits and potential side effects of the drug, including the risk of agranulocytosis and the need for regular blood monitoring.
- Start clozapine at a low dose (12.5 mg daily or less) and increase gradually, following the schedule suggested by the summary of product characteristics. Adjust the dose to achieve the optimal clinical response, while minimizing side effects.
- Monitor the physical health of people taking clozapine, including weight, blood pressure, blood glucose, and lipid levels, as well as signs of constipation, excessive sedation, and seizures.
- If clozapine is ineffective or not tolerated, review the diagnosis and consider a trial of another antipsychotic drug, either on its own or in combination with clozapine.
- If the person has persistent positive symptoms despite adequate trials of antipsychotic drugs, offer cognitive behavioral therapy (CBT) and family intervention, and review the person’s adherence to medication and any substance misuse.
Treatment Options for Treatment-resistant Schizophrenia
The main treatment for TRS is clozapine, a second-generation antipsychotic drug that has proven efficacy and superiority over other antipsychotics for TRS. Clozapine works by modulating the activity of dopamine, serotonin, and other neurotransmitters in the brain, and by reducing neuroinflammation and oxidative stress. Clozapine can improve the positive, negative, cognitive, and affective symptoms of TRS, and reduce the risk of suicide and hospitalization. However, clozapine also has some serious side effects, such as agranulocytosis, which is a potentially fatal condition that lowers the white blood cell count and increases the risk of infections. Therefore, clozapine requires regular blood monitoring and strict adherence to treatment.
TRS can cause various complications that affect the physical, mental, and social well-being of the patients and their caregivers. Some of the complications of TRS include:
- Physical health problems: TRS can increase the risk of developing various physical health problems, such as cardiovascular disease, diabetes, obesity, metabolic syndrome, and movement disorders. These problems may be caused by the symptoms of TRS, the side effects of the medications, or lifestyle factors, such as poor diet, physical inactivity, smoking, and substance abuse.
- Mental health problems: TRS can worsen the mental health of the patients, causing more depression, anxiety, mood swings, suicidal ideation, and self-harm. These problems may be caused by the distress and stigma of having TRS, the lack of social support, or the comorbidity of other psychiatric disorders, such as bipolar disorder, personality disorder, or post-traumatic stress disorder.
- Social and occupational problems: TRS can impair the social and occupational functioning of the patients, leading to more isolation, loneliness, discrimination, unemployment, poverty, homelessness, and criminality. These problems may be caused by the cognitive and negative symptoms of TRS, low self-esteem and self-efficacy, or the lack of access to education, training, and rehabilitation services.
Therapeutic Approaches for Treatment-Resistant Schizophrenia
In addition to pharmacological treatment, TRS may benefit from various psychological and psychosocial therapies that aim to enhance the coping skills, functioning, and quality of life of the patients and their caregivers. Some of the therapies that may help TRS include:
- Cognitive-behavioral therapy (CBT): CBT is a form of psychotherapy that helps patients identify and challenge their distorted thoughts and beliefs, and replace them with more realistic and positive ones. CBT can also help patients manage their emotions, cope with stress, and improve their self-esteem and self-care.
- Family therapy: Family therapy is a form of psychotherapy that involves the family members of the patients, and helps them understand, communicate, and support each other better. Family therapy can also help the family members cope with the burden and stress of caring for a person with TRS, and reduce the conflict and tension in the family.
- Social skills training: Social skills training is a form of psychoeducation that teaches the patients how to interact and communicate with others effectively, and how to develop and maintain social relationships. Social skills training can also help the patients improve their social cognition, such as their ability to recognize and interpret social cues, emotions, and intentions.
- Cognitive remediation: Cognitive remediation is a form of cognitive training that aims to improve the cognitive functions of the patients, such as attention, memory, executive functions, and problem-solving. Cognitive remediation can also help the patients enhance their learning and academic performance, and increase their chances of finding and keeping a job.
TRS is a complex and challenging condition that affects a significant proportion of people with schizophrenia and requires a comprehensive and individualized approach to treatment and care. TRS can be defined as a failure to respond to standard antipsychotic medications and can cause more severe and persistent symptoms, and more physical, mental, and social complications.
The main treatment for TRS is clozapine, a second-generation antipsychotic drug that has proven efficacy and superiority over other antipsychotics, but also has some serious side effects that require regular monitoring. TRS may also benefit from various psychological and psychosocial therapies that can enhance the coping skills, functioning, and quality of life of the patients and their caregivers. TRS is a condition that deserves more attention and research, as it has a significant impact on the lives of patients, their families, and society.
(1) Treatment-resistant schizophrenia: Causes, symptoms, and more.
(2) What Is Treatment-Resistant Schizophrenia? – WebMD.
(3) Clinical indicators of treatment-resistant psychosis.
(4) Schizophrenia Treatment: Medication, Therapy, and Self-Care – Psych Central.
Ugonjwa wa schizophrenia unaoweza kushindwa na matibabu (TRS) ni ugonjwa unaoathiri karibu theluthi moja ya watu walio na ugonjwa wa schizophrenia, ambao hawajibu vizuri kwa dawa za kawaida za kuzuia ugonjwa wa akili. TRS ni changamoto kubwa kwa usimamizi na utabiri wa schizophrenia, kwani inahusishwa na dalili kali zaidi, ubora wa maisha mbaya, hatari ya kujiua, na gharama za huduma ya afya. Katika makala hii, tutazungumzia ufafanuzi, dalili na dalili, sababu, utambuzi, matibabu, matatizo, na matibabu ya TRS. Ugonjwa wa Schizophrenia Unaokataa Matibabu Ni Nini? TRS ni kutofaulu kwa kupata misaada ya kutosha ya dalili baada ya kujaribu angalau dawa mbili za antipsychotic za kipimo cha kutosha na muda, kama ilivyoelezwa na daktari. Hata hivyo, hakuna makubaliano juu ya vigezo sahihi au muda wa kugundua TRS, na masomo tofauti yanaweza kutumia ufafanuzi tofauti. Baadhi ya mambo ambayo yanaweza kuathiri utambuzi wa TRS ni pamoja na aina, kipimo, na muda wa dawa za antipsychotic, ukali na muda wa dalili, kufuata matibabu, uwepo wa comorbidities, na vigezo vya majibu. Dalili na Dalili Kuu Ni Zipi? Dalili za TRS ni sawa na zile za schizophrenia, lakini ni za kudumu na zenye kulemaza. Madhara hayo yanatia ndani dalili nzuri kama vile kupotea kwa fahamu, kupotea kwa fahamu, na usemi na tabia zisizo na utaratibu; dalili mbaya kama vile kutojali, kutokuwa na furaha, na kujitenga na watu; na dalili za utambuzi kama vile kupungua kwa uangalifu, kumbukumbu, na utendaji wa utendaji. TRS pia inaweza kusababisha dalili za kihisia, kama vile unyogovu, wasiwasi, na mabadiliko ya hisia; na dalili za mwili, kama vile kuongezeka kwa uzito, ugonjwa wa kimetaboliki, na matatizo ya mwendo. Ugonjwa wa Schizophrenia Unaoweza Kukabiliana na Matibabu Unatokeaje? Sababu za TRS hazijulikani kikamili, lakini huenda zikawa na mambo mengi ya kibiolojia, kisaikolojia, na ya mazingira. TRS inaweza kutokea kutokana na kutokuwa na usawa au kutofanya kazi kwa neurotransmitters mbalimbali katika ubongo, kama vile dopamine, glutamate, serotonin, na gamma-aminobutyric asidi (GABA). Vipengele hivyo vina jukumu katika kudhibiti hisia, utambuzi, utambuzi, na tabia, na vinaweza kuathiriwa na mabadiliko ya maumbile, mabadiliko ya epigenetic, au ushawishi wa mazingira. TRS inaweza kuhusishwa na uvimbe wa muda mrefu katika ubongo na mfumo wa neva, ambao unaweza kusababishwa na maambukizo, mkazo, majeraha, au magonjwa ya autoimmune. Uvimbe wa neva unaweza kuharibu chembe za ubongo na mzunguko, na kubadilisha mfumo wa kinga na kizuizi cha damu-ubongo, na kusababisha neurodegeneration na neurotoxicity. - Subtype ya schizophrenia: TRS inaweza kuwakilisha subtype tofauti ya schizophrenia, na kozi tofauti ya ugonjwa, utabiri, na majibu ya matibabu. TRS inaweza kugawanywa katika aina mbili: TRS ya msingi, ambayo inapatikana tangu mwanzo wa schizophrenia na ni sugu zaidi kwa matibabu, na TRS ya sekondari, ambayo huendelea kwa muda na ni sugu zaidi kwa matibabu. Ugonjwa wa TRS unategemea uamuzi wa kliniki wa daktari wa magonjwa ya akili, ambaye atathmini historia ya mgonjwa, dalili, majibu ya matibabu, na mambo mengine yanayohusiana. Kwa mfano, kuna vipimo vya dalili kama vile Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), na Global Assessment of Functioning (GAF). Daktari wa magonjwa ya akili anaweza pia kuagiza uchunguzi fulani ili kuondoa visababishi vingine vinavyoweza kusababisha dalili hizo, kama vile hali za afya, matumizi mabaya ya dawa za kulevya, au athari za dawa. TRS (Treatment-Resistant Schizophrenia) ni hali ambayo watu wenye ugonjwa wa schizophrenia hawajibu vizuri kwa angalau dawa mbili tofauti za antipsychotic. "Kama ilivyoelezwa katika Mwongozo wa TRS wa Taasisi ya Kitaifa ya Huduma ya Afya (NICE), ""Kutoa clozapine kwa watu wazima walio na schizophrenia ambao ugonjwa wao haujibu kwa kutosha kwa matibabu licha ya matumizi ya mfululizo ya kipimo cha kutosha cha angalau dawa mbili tofauti za antipsychotic.""" Angalau moja ya dawa lazima iwe antipsychotic ya kizazi cha pili isiyo ya clozapine. Kabla ya kuanza kutumia clozapine, mwambie mtu huyo kuhusu faida na athari za dawa hiyo, ikiwa ni pamoja na hatari ya agranulocytosis na haja ya kufuatilia damu mara kwa mara. Kuanza na clozapine katika kipimo cha chini (12.5 mg au chini) na kuongeza hatua kwa hatua, kufuatia ratiba iliyopendekezwa na muhtasari wa sifa za bidhaa. Badilisha kipimo ili kufikia majibu bora ya kliniki, wakati kupunguza athari za upande. - Angalia afya ya mwili ya watu wanaotumia clozapine, ikiwa ni pamoja na uzito, shinikizo la damu, sukari ya damu, na viwango vya lipid, pamoja na ishara za constipation, sedation kupita kiasi, na mshtuko. - Kama clozapine ni ineffective au si kuvumiliwa, upya utambuzi na kuzingatia jaribio la dawa nyingine antipsychotic, ama peke yake au katika mchanganyiko na clozapine. Ikiwa mtu ana dalili za kudumu za chembechembe licha ya majaribio ya kutosha ya dawa za antipsychotic, kutoa tiba ya tabia ya utambuzi (CBT) na uingiliaji wa familia, na kukagua kufuata kwa mtu kwa dawa na matumizi mabaya ya dawa yoyote. Tiba ya TRS ni dawa ya pili ya antipsychotic, ambayo imethibitishwa kuwa na ufanisi na ubora juu ya antipsychotics nyingine. Clozapine hufanya kazi kwa kurekebisha utendaji wa dopamine, serotonini, na neurotransmitters nyingine katika ubongo, na kwa kupunguza neuroinflammation na mkazo wa oxidative. Clozapine inaweza kuboresha dalili za TRS, na kupunguza hatari ya kujiua na kulazwa hospitalini. Kwa upande mwingine, clozapine ina athari mbaya za athari za agranulocytosis, ambayo inaweza kusababisha kifo kwa sababu ya kupungua kwa idadi ya chembe nyeupe za damu na kuongezeka kwa hatari ya maambukizi. Kwa hiyo, clozapine inahitaji uchunguzi wa kawaida wa damu na kufuata kwa ukali matibabu. TRS inaweza kusababisha matatizo mbalimbali ambayo huathiri afya ya kimwili, kiakili, na kijamii ya wagonjwa na watunzaji wao. Matatizo ya TRS ni pamoja na: Matatizo ya afya ya mwili: TRS inaweza kuongeza hatari ya kuendeleza matatizo mbalimbali ya afya ya mwili, kama vile ugonjwa wa moyo, kisukari, unene, ugonjwa wa kimetaboliki, na matatizo ya harakati. Matatizo haya yanaweza kusababishwa na dalili za TRS, athari za dawa, au mambo ya mtindo wa maisha, kama vile lishe mbaya, kutofanya mazoezi, kuvuta sigara, na matumizi mabaya ya dawa. TRS inaweza kuharibu afya ya akili ya wagonjwa, na kusababisha unyogovu zaidi, wasiwasi, mabadiliko ya hisia, mawazo ya kujiua, na kujidhuru. Matatizo haya yanaweza kusababishwa na shida na chanya ya kuwa na TRS, ukosefu wa msaada wa kijamii, au ugonjwa wa magonjwa mengine ya akili, kama vile ugonjwa wa bipolar, ugonjwa wa utu, au ugonjwa wa shida ya baada ya majeraha. Matatizo ya kijamii na ya kazi: TRS inaweza kudhoofisha utendaji wa kijamii na wa kazi wa wagonjwa, na kusababisha kutengwa zaidi, upweke, ubaguzi, ukosefu wa ajira, umaskini, ukosefu wa makazi, na uhalifu. Matatizo haya yanaweza kusababishwa na dalili za utambuzi na hasi za TRS, kujidharau na ufanisi wa kibinafsi, au ukosefu wa upatikanaji wa huduma za elimu, mafunzo na ukarabati. TRS inaweza pia kutajwa kama matibabu ya matibabu ya kisaikolojia na ya kisaikolojia ambayo yanalenga kuboresha ustadi wa kukabiliana na hali, utendaji, na ubora wa maisha ya wagonjwa na watunzaji wao. Tiba ya utambuzi-mwenendo (CBT) ni aina ya matibabu ya kisaikolojia ambayo husaidia wagonjwa kutambua na changamoto mawazo yao yaliyopotoka na imani, na kuzibadilisha na zile halisi na chanya. CBT pia inaweza kuwasaidia wagonjwa kusimamia hisia zao, kukabiliana na mkazo, na kuboresha kujithamini na kujitegemea. - Tiba ya familia: Tiba ya familia ni aina ya matibabu ya kisaikolojia ambayo inahusisha wanafamilia wa wagonjwa, na kuwasaidia kuelewa, kuwasiliana, na kuunga mkono kila mmoja vizuri zaidi. Tiba ya familia pia inaweza kusaidia washiriki wa familia kukabiliana na mzigo na mkazo wa kumtunza mtu aliye na TRS, na kupunguza mgogoro na mvutano katika familia. Mafunzo ya ustadi wa kijamii ni aina ya psychoeducation ambayo hufundisha wagonjwa jinsi ya kuingiliana na kuwasiliana na wengine kwa ufanisi, na jinsi ya kuendeleza na kudumisha mahusiano ya kijamii. Mafunzo ya ustadi wa kijamii pia yanaweza kusaidia wagonjwa kuboresha utambuzi wao wa kijamii, kama vile uwezo wao wa kutambua na kutafsiri ishara za kijamii, hisia, na makusudi. Matibabu ya utambuzi (Cognitive remediation) ni aina ya mazoezi ya utambuzi ambayo yana lengo la kuboresha kazi za utambuzi za wagonjwa, kama vile tahadhari, kumbukumbu, kazi za mtendaji, na kutatua matatizo. Matibabu ya utambuzi pia yanaweza kusaidia wagonjwa kuboresha ujifunzaji wao na utendaji wa kitaaluma, na kuongeza nafasi zao za kupata na kuweka kazi. TRS ni hali ngumu na ya changamoto ambayo huathiri idadi kubwa ya watu walio na schizophrenia na inahitaji mbinu ya kina na ya kibinafsi ya matibabu na utunzaji. TRS inaweza kufafanuliwa kama kushindwa kujibu dawa za kawaida za antipsychotic na inaweza kusababisha dalili kali zaidi na za kudumu, na matatizo zaidi ya kimwili, kiakili na kijamii. Tiba ya msingi ya TRS ni clozapine, dawa ya pili ya antipsychotic ambayo imethibitishwa kuwa na ufanisi na ubora juu ya antipsychotics nyingine, lakini pia ina athari mbaya za upande ambazo zinahitaji ufuatiliaji wa kawaida. TRS pia inaweza kufaidika na matibabu mbalimbali ya kisaikolojia na kisaikolojia ambayo yanaweza kuboresha ujuzi wa kukabiliana, utendaji, na ubora wa maisha ya wagonjwa na watunzaji wao. TRS ni hali ambayo inastahili uangalifu zaidi na utafiti, kwani ina athari kubwa kwa maisha ya wagonjwa, familia zao, na jamii. (1) Schizophrenia isiyopinga matibabu: Sababu, dalili, na mengineyo. (2) Ugonjwa wa Schizophrenia Unaokataa Matibabu Ni Nini?  WebMD. (3) Viashiria vya kliniki vya ugonjwa wa akili usioweza kutibiwa. (4) Matibabu ya Schizophrenia: Dawa, Tiba, na Kujitunza <unk> Psych Central.