It has been estimated that between 10 and 60% of patients resistant or intolerant with other antipsychotic drugs respond to clozapine.The side effects mentioned above are inevitably an impediment to its common use. Naltrexone is indicated for alcohol and opioid use disorder. They were considered to be refractory to phenothiazines. Many people with SCZ do not achieve a satisfactory treatment response to their initial antipsychotic drug treatment. Chronicity has often been misconstrued with treatment-resistance. The major side effects are a) agranulocytosis; b) metabolic side effects; c) myocarditis; d) seizures; e) severe constipation with gastrointestinal complications such as intestinal obstruction, bowel perforation, paralytics ileus and toxic megacolon; and f) sialorrhea. There are case reports of olanzapine, used for schizophrenia, causing RLS. The drugs have opposite effects on the dopamine receptor.Clonidine is used off-label treatment for ADHD, but there are reports of MDD in up to about 2.3% of people taking it. As it stands now, deconstructing clozapine’s unique pharmacology may offer ‘light at the end of the tunnel’ for patients who are clozapine intolerant or non-responders. Though clozapine often represents the best hope for recovery, it is associated with severe and enduring adverse reactions that may delay its prescription and increase morbidity and mortality. Combination drug therapy is a type of treatment that many doctors and psychiatrists have been increasingly utilizing during the past decade. Patients have been fully compliant. Naltrexone does not block every pain medication, however. Furthermore, two epidemiological studies have shown that clozapine has the lowest mortality rate among antipsychotics.Nevertheless, even supported by the literature as the best-known antipsychotic in terms of efficacy and rates of response, a sizeable number of patients remain resistant to clozapine therapy and continue as symptomatic and dysfunctional. At least in isolated cases, the combination of olanzapine and amisulpride (Ami-olan combination) is worth considering for TRS patients who are reluctant to go on to clozapine therapy or in instances when clozapine failed, or patents dropped out. More investigation of schizophrenic illness is the only way forward. Only time will tell whether this combination will become an important part of clinical practice in future or will be ruled out as just another dual antipsychotic therapy.The aetiology of SCZ remains obscure. Alprazolam is indicated for anxiety, but can cause sleepiness, memory impairment, and cognitive disorder. Oxybutynin is indicated for bladder muscle dysfunction, but it is associated with a decline in greater decline in mini-mental state examination scores over 2 years. To mention a few antipsychotics, amisulpride and aripiprazole are atypical antipsychotics ordinarily used in combination with clozapine. Mirtazapine blocks the alpha-2a receptor, but the clonidine stimulates it.Clozapine is indicated for schizophrenia, but it is linked to the emergence or worsening of obsessions, because it stimulates the receptor involved in OCD. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as ropinirole. Consideration of the effect of long-term progress and physical consequence of medications are central to therapy selection. If that drug failed, they mig… Olanzapine–amisulpride combination Side effects are more common with higher doses. Combination of antipsychotics is not a panacea or a permanent solution for TRS. Propranolol, a hypertension drug, can impair learning performance.Ropinirole is indicated for restless leg syndrome (RLS), but can cause psychosis an 8% of Parkinson disease patients, or even in people taking it purely for RLS. That goes for antidepressants, antipsychotics, and anti-anxiety medications, he noted. Yet, fixed combinations of drugs are common in medicine and at one time were common in psychiatry. NICE offers very little guidance on clozapine resistant cases of SCZ. An example is small doses of an antipsychotic in combination with an antidepressant for treating major depression; this lost popularity because of side effects. Another antipsychotic combination may become necessary as an option for TRS patients who cannot be treated with clozapine for various reasons. 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