Patients treatment resistant

Revicki DA, Luce BR, Weschler JM et al (1990). Cost-effectiveness of clozapine for treatment-resistant schizophrenic patients. Hosp Community Psychiatry 850-69. 

The drug was subsequently reintroduced for treatment-resistant or treatment-intolerant patients in the UK and USA in 1990. The drug is completely free of extrapyramidal side effects but has to be monitored for the development of neutropenia and agranulocytosis. Other problems include sialorrhoea, sedation, reduction in seizure... 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

Vagus nerve stimulation (VNS) may be used for adult patients with treatment-resistant depression. A pulse generator is surgically implanted under the skin of the left chest, and an electrical lead connects the generator to the left vagus nerve. Stimulation of this nerve sends signals to the brain. This therapy is intended to be used along with traditional therapies, such as pharmacotherapy and ECT.20... 

There is concern regarding administration of dexamethasone to patients with pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, for which vancomycin would be required. Animal models indicate that concurrent steroid use reduces vancomycin penetration into the CSF by 42% to 77% and delays CSF sterilization due to reduction in the inflammatory response.23 Treatment failures have been reported in adults with resistant pneumococcal meningitis who were treated with dexamethasone, but the risk-benefit of using dexamethasone in these patients cannot be defined at this time. Animal models indicate a benefit of adding rifampin in patients with resistant pneumococcal meningitis whenever dexamethasone is used.21,23... 

Erythromycin is considered the optimal drug for treatment of Campylobacter infections. The rate of resistance of Campylobacter to erythromycin remains low. Other advantages of this drug include ease of administration, low cost, lack of major toxicity, and narrow spectrum of activity.14 The recommended dosage for adults is 250 mg orally four times daily or 500 mg orally twice daily for 5 to 7 days. For very ill patients, treatment with gentamicin, imipenem, cefotaxime, or chloramphenicol is indicated, but susceptibility tests should be performed. 

Acute HIV Infection Diagnosis of acute HIV infection is difficult, since many patients are asymptomatic, or have nonspecific clinical symptoms similar to other common respiratory infections. If acute HIV infection is suspected, HIV antibody tests and a plasma HIV RNA concentration should be obtained. A clear diagnosis is made when an HIV antibody test is negative and the plasma HIV RNA concentration is high. There are limited outcomes data for treating acutely infected patients. Treatment of acute infection can decrease the severity of acute disease and decrease the viral set point this may decrease progression rates and reduce the rate of viral transmission.18-22 Limitations include an increased risk of chronic drug-induced toxicides and the development of viral resistance. 

Patients respond variably to the more than 20 FDA-approved antidepressants Only 60-70% of patients show significant response to any specific antidepressant, and there is no predictor of response to those drugs. Thus, the development of novel therapies should be geared to solve two important issues in treatment treatment resistance or refractoriness to current antidepressants, and medication compliance. 

Approximately 30-40% of patients will not respond to a given antidepressant and 60-75% may fail to achieve complete remission [16]. Consequently, in its least restricted definition, treatment resistance could be detected in the majority of depressed patients under treatment. Moreover, prior treatment failure negatively influences the response to subsequent antidepressant treatment, decreasing the odds of treatment response by a factor of 15-20% for each failed treatment [17]. The delayed onset of symptom relief (which takes three to eight weeks to occur) and the presence of adverse drug reactions contribute significantly to low treatment compliance. 

Gionchetti P, Rizzello F, Venturi A, Ugolini F, Rossi M, Brigidi P, Johansson R, Ferrieri A, Poggioli G, Campieri M Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis. Aliment Pharmacol Ther 1999 13 713-718. 

In a small study ciprofloxacin was shown to be effective in association with standard treatment in patients with resistant disease [40], The results of this study were challenged by a controlled study in which ciprofloxacin (1 g/day) was associated with budesonide (9 mg/day) in ileocolic active CD. No difference was found compared to placebo, but surprisingly the overall response in both groups was lower than that reported in previous studies with budesonide [41],... 

Phenelzine, an MAOI, is effective, but is reserved for treatment-resistant patients because of dietary restrictions, potential drug interactions, and adverse effects. 

The combination of carbamazepine with lithium, valproate, and antipsychotics is often used for manic episodes in treatment-resistant patients. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

Most treatment-resistant depressed patients have received inadequate therapy. Issues to be considered in patients who have not responded to treatment include the following (1) Is the diagnosis correct (2) Does the patient have a psychotic depression (3) Has the patient received an adequate dose and duration of treatment (4) Do adverse effects preclude adequate dosing (5) Has the patient been compliant with the prescribed regimen (6) Was treatment outcome measured adequately (7) Is there a coexisting or preexisting medical or psychiatric disorder (8) Was a stepwise approach to treatment used (9) Are there other factors that interfere with treatment ... 

A recently filed case in Pennsylvania illustrates a possible new face for liability (Cassidy v. SmithKline Beecham, 1999). The plaintiff claims that the manufacturer of a vaccine for Lyme disease should have warned physicians and patients in its advertisements that 30% of the population ran the risk of developing "treatment-resistant Lyme arthritis" because their particular genotype interacted adversely with the vaccine. This duty to warn is based not in product liability doctrine, but on negligence. 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

In addition to being effective in the treatment of schizophrenia, clozapine also is effective in the treatment of the manic phase of bipolar disorder. Although not a first-line treatment for mania, clozapine is useful for patients who are not responding well to more traditional treatments. Finally, clozapine is the one antipsychotic proven to help treatment-resistant schizophrenia. Fully one-third of patients who do not respond to other antipsychotics will respond to clozapine. 

Clozapine can certainly be a difficult and expensive medication to take. However, for the treatment-resistant patient with schizophrenia, clozapine is often well worth the trouble. 

Only after a patient has failed two adequate antipsychotic trials should clozapine or augmentation with a second medication be considered. Refer to Section 4.7 for more information on handling treatment resistance. 

Psychosurgery. Case series have been reported of patients with severe treatment resistant social anxiety disorder undergoing surgical procedures including capsu-lotomy and endoscopic transthoracic sympathectomy. Given the limited evidence... 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

Treatment Resistance. Many patients with PTSD remain symptomatic despite antidepressant treatment and psychotherapy. Thus, augmentation strategies are... 

It has been estimated that at least 30% of patients with major depression fail to respond to a 6-week course of a TCA antidepressant. A major problem arises however in the definition of "treatment resistance". To date, there appears to be no internationally acceptable definition of the condition. A practical definition which many clinicians find useful is that treatment resistance occurs when the patient fails to respond to ... 

---