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    By I. Ford. Aquinas College.

    Several trials have been undertaken to determine the efcacy of BV treatment among pregnant women buy generic modafinil 200mg on-line. Two tri- HIV Infection als demonstrated that metronidazole was efcacious during BV appears to recur with higher frequency in HIV-positive pregnancy using the 250-mg regimen (338 discount modafinil 100mg line,339); however, women (352). Patients who have BV and also are infected with metronidazole administered at 500 mg twice daily can be used. HIV should receive the same treatment regimen as those who One trial involving a limited number of participants revealed are HIV negative. Some women have symptoms between metronidazole use during pregnancy and teratogenic characterized by a difuse, malodorous, yellow-green vaginal or mutagenic efects in newborns (342,343). However, many women have the antimicrobial agent used to treat pregnant women, oral minimal or no symptoms. Because of the high prevalence therapy is preferred because of the possibility of subclinical of trichomoniasis in clinical and nonclinical settings upper-genital–tract infection. Screening for Recommended Regimens for Pregnant Women T. OR Diagnosis of vaginal trichomoniasis is usually performed Clindamycin 300 mg orally twice a day for 7 days by microscopy of vaginal secretions, but this method has a Vol. FDA-cleared tests for trichomoniasis in women include Recommended Regimens OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, Massachusetts), an immunochromatographic Metronidazole 2 g orally in a single dose capillary fow dipstick technology, and the Afrm VP III OR (Becton Dickenson, San Jose, California), a nucleic acid probe Tinidazole 2 g orally in a single dose test that evaluates for T. Each of these tests, which are performed on vaginal secretions, Alternative Regimen have a sensitivity of >83% and a specifcity of >97%. Both Metronidazole 500 mg orally twice a day for 7 days* tests are considered point-of-care diagnostics. Te results of * Patients should be advised to avoid consuming alcohol during treatment the OSOM Trichomonas Rapid Test are available in approxi- with metronidazole or tinidazole. Abstinence from alcohol use should mately 10 minutes, whereas results of the Afrm VP III are continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole. Although these tests tend to be more sensitive than those requiring vaginal wet preparation, false positives might occur, especially in populations with a Te nitroimidazoles comprise the only class of drugs use- low prevalence of disease. Of Culture is another sensitive and highly specifc commer- these drugs, metronidazole and tinidazole are available in the cially available method of diagnosis. Among women in whom United States and are cleared by the FDA for the treatment of trichomoniasis is suspected but not confrmed by microscopy, trichomoniasis. In randomized clinical trials, the recommended vaginal secretions should be cultured for T. While the metronidazole regimens have resulted in cure rates of approxi- sensitivity of a Pap test for T. Randomized controlled trials compar- PCR assay for detection of gonorrhea and chlamydial infec- ing single 2-g doses of metronidazole and tinidazole suggest tion (Amplicor, manufactured by Roche Diagnostic Corp. Several other topically applied antimicrobials ASR found sensitivity ranging from 74%–98% and specifcity occasionally have been used for treatment of trichomoniasis; of 87%–98% (357–359). Laboratories that use the Gen-Probe however, these preparations likely are no more efective than APTIMA Combo2 test for detection of N. Because of the high rate of reinfection among patients in In men, wet preparation is not a sensitive test, and no whom trichomoniasis was diagnosed (17% were reinfected approved point-of-care tests are available. Culture testing within 3 months in one study), rescreening for T. While to infect oral sites, and rectal prevalence appears low in MSM most recurrent T. Low-level metronidazole resistance has natal morbidity. Although some trials suggest the possibility of been identifed in 2%–5% of cases of vaginal trichomoniasis increased prematurity or low birth weight after metronidazole (362,363), but high-level resistance only rarely occurs. Treatment respond to tinidazole or higher doses of metronidazole. In addition, many infection of the newborn and further sexual transmission. All symptomatic pregnant women should with metronidazole 500 mg orally twice daily for 7 days. For not only be considered for treatment regardless of pregnancy patients failing this regimen, treatment with tinidazole or stage, but be provided careful counseling regarding condom metronidazole at 2 g orally for 5 days should be considered. If use and the continued risk of sexual transmission.

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    Following the success of carbamazepine as a mood stabilizer cheap 200 mg modafinil fast delivery, sodium valproate was found to be effective buy modafinil 200mg amex. In both acute mania and long term maintenance, sodium valproate is as effective as lithium and carbamazepine (Macritchie et al, 2004; Cipriani et al, 2013). It may be superior to lithium in the treatment of rapid cycling and mixed mania. In comparison to lithium, sodium valproate treatment provides comparable medical costs, clinical and quality of life outcomes (Revicki et al, 2005), with generally fewer side effects. The mode of action is uncertain; as with other mood stabilizers, there is blocking of sodium channels. In addition, there is potentiation of gamma aminobutyric acid (GABA) and effects on intracellular protein regulation. Animal studies show sodium valproate is neuroprotective, protecting neurones against glutamate induced excitotoxicity (Chuang, 2005) and promotes neurogenesis and neurite growth (Chen & Manji, 2006). Psychiatric uses  Acute management of mania  Prophylactic management of mania  Schizoaffective disorder  Management of bipolar depression (No controlled studies) Side-effects Common  Nausea  Vomiting  Abdominal pain  Diarrhoea  Tremor  Somnolence  Dizziness  Weight gain  Hair loss (reversible on discontinuation of valproate) Pridmore S. Haemodialysis may be necessary to eliminate the drug. Sodium valproate is associated with a 1% risk of neural tube defects, such as spina bifida when taken during the first trimester of pregnancy. Other congenital malformations have been reported, and the overall risk may be as high as 11% (Ernst and Goldberg, 2002). Gentile (2012) states risk to the unborn is unacceptable. Sodium valproate passes into the breast milk at less than 10% of the serum concentration. The effects on the nursing child are uncertain, but the risk is considered to be very low. Drug interactions Amitriptyline (TCA) and fluoxetine (SSRI) may increase valproate concentration, possibly by inhibiting valproate metabolism. Aspirin may elevate the free fraction of valproate, by displacing from protein-binding sites, thereby increasing the effects on the central nervous system. Valproate can displace diazepam, carbamazepine and warfarin, thereby increasing the activity of these drugs. Dosage and monitoring Blood count, liver function tests, and if appropriate, pregnancy testing. The starting dose is 250-1000 mg per day, in two divided doses. Dose can be increased every 2-3 days, depending on response and tolerance. In acute mania, oral loading of 20mg/kg can be given on the first day, to achieve rapid therapeutic levels. Patients who are not acutely manic may have difficulty tolerating this load. The usual therapeutic concentration is 50-150 micrograms/mL (blood drawn 12 hours after the last dose). It appears (in contrast to the other mood stabilizers) to be more effective in preventing relapse into depression than relapse into mania (Calabrese et al, 2003; Gitlin and Frye 2012). Lamotrigine is a first line drug in the treatment of bipolar depression. A rash occurs in up to 6% of patients, and is a cause of discontinuation. Recent work suggests that the therapeutic response to lamotrigine is dependent on plasma concentration (Kagawa et al, 2014). Commence with caution: 25 mg/day for 2 weeks, at week 3 increase to 50 mg/day, at week 5, increase to 100 mg per day at week 6, 200 mg/day (maximum dose).

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    Approximately 25% of first-episode patients this literature generally supports their use for acute and exhibit depression modafinil 200mg generic, although estimates of the incidence of maintenance treatment of depressive symptoms in stable comorbid depression vary widely according to choice of di- patients (264 cheap modafinil 200 mg amex,265). Augmentation with selective serotonin agnostic criteria (251–253). The prevalence of depression reuptake inhibitors has been studied primarily as a treat- as defined by moderate scores on depression rating scales ment for negative symptoms—use of these agents in schizo- ranges between 25% and 50% in chronic patients (252, phrenia patients with depression is not well studied. Although considerable overlap exists between symp- larly, addition of antidepressants to atypical agents has not toms of depression and certain negative symptoms (e. Cognitive Symptoms Conventional antipsychotics tend to have little effect on comorbid depression, although anxiety and depression asso- Antipsychotic Monotherapy ciated with acute psychotic exacerbation frequently respond A wide range of cognitive deficits are usually present at the to neuroleptic monotherapy (257,258). However, dys- time of the first psychotic episode (266) and remain stable Chapter 56: Therapeutics of Schizophrenia 789 or only slowly progressive during the course of the illness, effects of atypical agents, particularly because excessive dos- independent of psychotic symptoms (267–269). Cognitive ing can impair performance on time-sensitive tasks and in- deficits are particularly prominent in patients meeting crite- crease anticholinergic exposure. The latter association may indicate Adjunctive Agents that cognitive deficits are a risk factor for tardive dyskinesia, Augmentation with glutamatergic agents has shown prom- or alternatively, that the neurotoxic mechanism responsible ise for cognitive deficits in schizophrenia (279). As noted, for irreversible motoric deficits also compromises cognitive glycine and D-serine improved ratings of cognitive func- functioning. Targeting cognitive impairments is now a tioning when added to conventional neuroleptics (241, major focus of drug development because cognitive deficits 280). Both agents improved the 'cognitive subscale' of the are powerful determinants of vocational and social function- PANSS compared to placebo, and D-serine was also associ- ing and may influence quality of life (36) more than psy- ated with improved performance on the Wisconsin Card chotic symptoms. These findings are of interest given that NMDA antag- The conventional neuroleptics produce small and incon- onists produce in normal subjects deficits in attention and sistent effects on cognitive functioning; sustained attention memory similar to those found in schizophrenia (281,282). Recent evidence in monkeys study that utilized formal cognitive testing, however (240). In a preliminary 4-week, placebo-controlled trial in- mal subjects, clozapine administered as a single 50-mg dose volving 19 schizophrenia patients, CX-516, a positive mod- worsened attention, concentration, and motor functioning ulator of the glutamatergic AMPA receptor, improved per- (275), presumably reflecting sedative and anticholinergic formance on tests of memory and attention when added to properties. Studies in patients with schizophrenia have clozapine (284). Effect sizes favoring CX-516 over placebo found either no effect following a switch to clozapine (276), were moderate to large (. In general, clozapine, olanzapine, and risperidone Psychosocial Treatments have demonstrated superior efficacy compared to conven- Although cognitive remediation treatments have long been tional agents on tests of verbal fluency, digit-symbol substi- used for brain-injured individuals, similar treatment ap- tution, fine motor function, and executive function (37, proaches targeting cognitive deficits in schizophrenia are 277). Atypical agents least affected measures of learning and relatively recent. In small studies in which schizophrenia memory (37). Enhanced performance with atypical agents patients practiced graduated cognitive exercises, perfor- could result, in part, from reduced parkinsonian side effects mance on laboratory measures of attention and memory because these tests all measure performance during a timed function improved, although the functional benefits of these trial (37). Methodologic issues limit comparisons between gains are not clear (285,286). Brenner and colleagues (287) atypical agents, however, preliminary evidence suggests that developed integrated psychological therapy (IPT), a cogni- risperidone may be more effective for visual and working tive remediation program in which cognitive exercises are memory than clozapine (277). In a 12-month, double-blind provided in a group format stressing the integration of cog- trial involving 55 schizophrenia patients randomly assigned nitive skills with social functioning. In a 6-month random- to olanzapine (mean dose 11 mg per day), risperidone (mean ized trial in which patients received IPT or supportive treat- dose 6 mg per day), or haloperidol (mean dose 10 mg per ment in addition to comprehensive psychiatric day), risperidone and olanzapine produced significantly rehabilitation, the IPT group displayed greater improve- greater improvement in verbal fluency compared to haloper- ment on the primary outcome measure of interpersonal idol, and olanzapine was superior to both haloperidol and problem solving and on a laboratory measure of attentional risperidone in effects on motor skills, nonverbal fluency, processing (288). This study was conducted prior to the and immediate recall (278). However, this finding is com- introduction of atypical antipsychotics. Following another plicated by the high incidence of anticholinergic administra- approach, Hogarty and Flesher (289) recently developed tion prior to the final cognitive assessment; anticholinergics cognitive enhancement therapy (CET), which combines in- were prescribed to 73% in the haloperidol group, 45% in teractive software and social group exercises to improve so- the risperidone group, and 15% in the olanzapine group. This As in efficacy studies for negative symptoms, dose equiva- approach is based on a neurodevelopmental model for cog- lency is an important factor in trials comparing cognitive nitive deficits in schizophrenia (290). Preliminary results 790 Neuropsychopharmacology: The Fifth Generation of Progress from a controlled 1-year trial of CET have also been encour- cant activation of heteroreceptors on target cells (300).

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