All Others
Home Up Fish Oil Atypicals: General Amisulpride Abilify Clozapine Zyprexa Seroquel Risperidone Geodon All Others Depot Medication Exercise Traditional Side-Effects

 
Allopurinol
Glycine
rTMS
Vitamins

A huge variety of medicines other than anti-psychotics have been tried on schizophrenia.  It appears a good idea to give all patients with schizophrenia at least 800 mcg of folate a day (see below under vitamins).  Allopurinol has recently been found helpful in two double-blind studies. Two other studies with diazoxide and dipyrimadole showed benefit and work in somewhat similar ways.  Allpurinal is inexpensive with a low level of side-effects and thus quite appealing.  Many anti-depressants help, especially for negative symptoms in studies with traditional anti-psychotics, although anti-depressants can also sometimes make psychotic symptoms worse.  Glycine has been repeatedly shown to be helpful for negative symptoms and is inexpensive, but not covered by prescription plans.  Fish oil or fish should also be used, although its benefits are probably minor.

ECT probably helps, but is expensive, the benefits short-lived, and causes unpleasant feeling of memory impairment.  Beta-blockers appear to help aggressive symptoms somewhat. Clonidine in multiple studies. Single studies find benefit with DHEA in women, divalproex, ginkgo, estradiol in women, rTMS, and valacyclovir in cytomegavirus positives.  rTMS looks worthwhile for hallucinations. There have been negative studies with divalproex, and estrogen.  The DHEA side-effect risk are too great for me to consider.

Ampakines: for Schizophrenia: A new family of meds being studied have glutaminergic effects at AMPA receptors. In a study of clozapine patients, an experimental drug helped memory and depression. J Clin Psychophar 01;21:484

Anti-Depressant: SSRI Lowers Negative Symptoms in Schizophrenia: Charite University Medicine Berlin , Germany . Int Clin Psychopharmacol. 2005 Jan;20(1):27-31. Ed: A growing number of studies have documented this phenomenon. 

Anti-Depressants: Imipramine: Helps Post-Psychotic Depression: DB PC study found long-term maintenance helped depression and also decreased psychotic relapses over 1 yr study in 24 pt. Siris, Al Einstein, Arch Gen Psych ’94;51:109

Anti-Depressants: Imipramine Helps Negative Symptoms: DB PC of patients on fluphenazine decanoate and negative or post-psychotic depressive symptoms. The use of antidepressants for negative symptoms in a subset of schizophrenic patients. Siris SG, Bermanzohn PC, Gonzalez A, Mason SE, White CV, Shuwall MA. Psychopharmacol Bull 1991;27(3):331-5

Anti-Depressants: Fluvoxamine Helps Negative Symptoms: DB PC SSRI Fluvoxamine vs maprotiline 25 pt 6wk found decrease in negative symptoms with fluvoxamine but not with maprotiline. Author says other studies show SSRIs help neg. Silver, Isreal, J Clin Psychopharm ’98;18:208; Fluoxetine helped too. Int Clin Psychopharm ’94;9:281; Another study found Trazodone helped.

Anti-Depressants: Fluvoxamine Adjunct to Haldol Helps Negative Symptoms, Increases Haldol: 12 schiz with negative symptoms on Haldol 6mg/d given fluvox 25 to 75 to 150 2 weeks each. Haldol levels increased 125% on 25mg and 160% on 150mg/d although no increase in EPS. Fluvoxamine dose-dependent interaction with haloperidol and the effects on negative symptoms in schizophrenia. Yasui-Furukori N, Kondo T, Mihara K, Inoue Y, Kaneko S. Psychopharmacology (Berl). 2003 Sep 4

Anti-Depressants: Reboxetine Didn't Help Negative Symptoms of Schizophrenia with Haldol in DB: A small 30 patient DB PC study didn't find benefit. Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study. Schutz G, Berk M. Int Clin Psychopharmacol. 2001 Sep;16(5):275-8

Anti-Depressants: Selegiline Helpful for Negative Symptoms: In a 12-week, DB PC study of the MAO Inhibitor anti-depressant selegiline vs. placebo added to antipsychotic medication for outpatients with schizophrenia with negative symptoms and no severe positive symptoms and no major depression,  negative symptoms were found to be significantly more improved in the patients who received selegiline. Global improvement scores also favored selegiline. Double-blind, placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia. Bodkin JA, Siris SG, et al. McLean Hospital, Harvard. Am J Psychiatry. 2005 Feb;162(2):388-90

Beta-Blockers: Pindolol Helps in DB of Aggressive Schiz: 30 male schizophrenic patients hospitalized in maximum security with 4+ aggressive incidents in prior 2 months each in a crossover PC DB study receiving 6 week pindolol and 6 weeks placebo. Aggression 0.6 vs. 1.5 against objects and 2.0 vs. 3.2 against persons with severity of incidents markedly reduced and no impact on PANSS scores. 3 patients stopped due to syncope, low BP, or bronchospasm. Caspi N et al: Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study. Int Clin Psychoph 01;;16:111-5, Israel

Beta-Blockers: Nadolol Didn't Help DB Aggressive Schiz: 34 male inpatients DB PC nadolol 80mg/d x 1 week to 120mg/d x 2 weeks. BPRS better after 1 week but by two weeks the advantage no longer significant. Hostility unaffected. No difference in akathesia. Allan E et al: Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients. J Clin Psyc 96;57:455-9. 

Beta-Blockers: Nadolol Helps Schizophrenic Aggression: A double-blind, placebo-controlled study of adjunctive nadolol (40-120 mg/day) in 41 patients, 29 of whom were schizophrenic, found a decline in the frequency of aggression compared with controls. Ratey JJ, Sorgi P, O'Driscoll GA, et al. Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. J Clin Psychiatry. 1992;53:41-46.

Beta-Blockers: Nadolol Tended to Help Violent Patients: In a report of a double-blind, placebo-controlled study of adjunctive nadolol (80-120 mg/day) in 30 violent inpatients, of whom 23 were schizophrenic, a trend was found demonstrating lower hostility for the active treatment group. Alpert M, Allan ER, Citrome L, Laury G, Sison C, Sudilovsky A. A double-blind, placebo-controlled study of adjunctive nadolol in the management of violent psychiatric patients. Psychopharmacol Bull. 1990;26:367-371

Carbamazepine: No Benefit for Negative Symptoms: DB PC 28 pt. Israel, Biol Psychiatry ’94;35:22

Carbamazepine: Meta-Analysis Finds No Clear Benefit: Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. J Clin Psychiatry 2002 Mar;63(3):218-24

Clonidine: Study shows Add-on Benefit: DB PC as add-on to Haldol. Clonidine is an alpha 2-adrenergic agonist. Maas, U Tx, J Clin Psychopharm ’95;15:361; Also a 1989 study found benefit in 4 of 13 schiz patients. Van Kammen, U Pitt, Psych Res 3/89;27:297. Two studies with alpha 2-adrenergic antag idazoxan also found benefit as an add on at 120 mg/d with 6 patients. Litman, NIMH, J Clin Psychopharm ’93;13:264.

DHEA: No Overall Benefit in Psychosis: In a DB PC study of 40 patients with chronic schizophrenia stabilized on olanzapine, DHEA (titrated up to 150mg) for 12-weeks, there was some improvement in negative symptoms, Parkinsonism and akathisia compared to baseline. However, more importantly, no change in psychosis as reflected by the PANSS. Analysis of clinical symptomatology, extrapyramidal symptoms and neurocognitive dysfunction following dehydroepiandrosterone (DHEA) administration in olanzapine treated schizophrenia patients: a randomized, double-blind placebo controlled trial. Strous RD, et al. Beer Yaakov, Israel. . Psychoneuroendocrin 2007 Feb;32(2):96-105.

DHEA Helped Some Symptoms But No Overall Benefit: In a 12-week DB PC crossover study of 62 inpatients and outpatients with schizophrenia, DHEA (200 mg/d) did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores, although it did results in a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline and in cognitive functions of visual sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia. Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. Ritsner MS, et al. Haifa, Israel. . J Clin Psychopharm 2006 Oct;26(5):495-9.

DHEA: Helps Negative, Depressive, & Anxiety Symptoms: DB PC 30 schiz with prominent negative symptoms 100mg/d 6 weeks. Significant improvement in negative symptoms (P<.001), as well as in depressive (P<.05) and anxiety (P<.001) symptoms in individuals receiving DHEA. This effect was especially noted in women. Israel. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, Weizman A. Arch Gen Psychiatry 2003 Feb;60(2):133-41

DHEA Linked to Negative Symptoms and Augmentation Said to Help: In a study of 10 adult male schizophrenics, 5 with predominantly positive symptoms (group I) and 5 with predominantly negative symptoms (group II), and 10 healthy matched controls, no significant differences in serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), estradiol, and cortisol were found between patients as a whole and controls. However, serum T and DHEAS levels were lower (P <0.05) in group II patients than in group I. Body hair and aggression scores also were lower (P <0.05) in group II. In a much larger sample, Shirayama showed that "moderate negative symptoms, but not low negative symptoms" correlated negatively with T (P <0.05), but positively with ACTH (P <0.05) and cortisol (P <0.01) levels in plasma. Neuroactive steroids, such as DHEAS, and other sex hormones, including their synthetic derivatives, may have an adjunctive role in reversing or slowing the progression of negative symptoms. "DHEA augmentation" improved "negative (P <0.01), depressive (P <0.05), and anxiety (P <0.01) symptoms." Negative correlation between negative symptoms of schizophrenia and testosterone levels. Goyal RO, et al. All India Institute of Medical Sciences, New Delhi, India. Ann N Y Acad Sci. 2004 Dec;1032:291-4.

Donepezil (Aricept); Rivastigmine (Exelon) No Benefit in Two Studies: In an 8-week DB PC study of 36 patients with schizophrenia, the addition of donezezil 10 mg/d was of no benefit for cognition or psychopathology. Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial. Freudenreich O, Herz L, et al. Harvard-MGH Schizophrenia Program. Psychopharmacology (Berl). 2005 Mar 19; Rivastigmine was also of no benefit in another double-blind study. Curr Med Res Opinion 2007 Mar;23(3):575-83. Ed: Cholinesterase inhibitors appear to have no role in the treament of schizophrenia.

ECT: Brief vs Ultra Brief Both Help: DB study 48 schiz 8 sessions found dramatic benefit maintained at 1 month without memory impairment. Pisvejc, J ECT ’98;14:68

ECT No Benefit Add-On: DB study with sham ECT control and ECT as add-on Rx to anti-psychotic found no added benefit in 30 new schizophreniform pts. Sarkar, India, Convul Ther ’94;10:271

ECT Equal to Meds: DB trial found 1wk faster improvement with ECT but equal thereafter and at 6 months. Abraham, India, Br J Psych ’87;151:152

Electroacupuncture as an Add-On: In a DB study of 90 schizophrenia patients, electroacupuncture was added to clozapine and clozapine alone. The total effective rate was 75% with added electroacupunture and 73% with clozapine alone. However, somatic complaint was lower and compliance was higher in the EA group. Short-term curative effect of electroacupuncture as an adjunctive treatment on schizophrenia. Feng-Ju Y, et al. Second Affiliated Hospital of Xinxiang Medical College, Henan, China. . Zhongguo Zhong Xi Yi He Za Zhi 2006 Mar;26(3):253-5. Ed: Electroacupunture is very similar to Cranial Electrostimulation.  It is easy and harmless.  However, I can't tell if it had any beneficial effect in this study.  It has been found helpful by itself for depression, fibromyalgia, and other conditions.

Estrogen: Might Help as Add-On: Females have later onset of schizophrenia than men. Also, 35% increase in admissions from 3 days before to 3 days after onset of menses. 36 women schizophrenics stable on risperidone were treated for 28 days with a placebo or estradiol patch 50 microg/d or 100 microg/d. Higher dose group had fewer psychotic symptoms at 28 days. Kulkarni, Arch Women Ment Health 11/02;5:99-104

Estrogen Didn't Help Schizophrenic Women: In a DB PC cross-over study of 46 hypoestrogenic women hospitalized for schizophrenia with an average age of 38, there was no added advantage to high or low dose estrogen in addition to standard anti-psychotic treatment. Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study. Bergemann N, Mundt C, et al. Ruprecht-Karls-University of Heidelberg, Germany. Schizophr Res. 2005 May 1;74(2-3):125-34

Galantamine No Significant Benefit: In a 12-week DB PC study of 24 patients stabilized on antipsychotic drugs (chlorpromazine equivalent dose of 1390 mg/day) for a minimum of 3 months, compared with placebo, galantamine produced a small and nonsignificant change in the cognitive measures, but the score for recognition on the Rey Complex Figure Test improved significantly in patients given galantamine (P<0.05). Of the several domains of cognitive functions assessed, galantamine tended to improve the score for recognition on the Hopkins Verbal Learning Test and for color on the Stroop Test (P<0.1), but these results were not statistically significant. The addition of galantamine to the conventional antipsychotic medication of patients with schizophrenia does not produce a change in the cognitive function or state of psychopathology. A 12-week, double-blind, placebo-controlled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Lee SW, et al. Inje University, Republic of Korea. Int Clin Psychopharm 2007 Mar;22(2):63-68.

Gluten Free Diet Might Help Some: 24 pts secure unit put on gluten free with reintroduction. Two patients improved off gluten then deteriorated with reintroduction. A double-blind gluten-free/gluten-load controlled trial in a secure ward population. Vlissides DN, Venulet A, Jenner FA. Br J Psychiatry 1986 Apr;148:447-52

Gluten Challenge No Impact: 8 chr schiz on gluten-cereal-milk free diet challenged DB PC with gluten cookies. Wheat gluten challenge in schizophrenic patients. Potkin SG, Weinberger D, Kleinman J, Nasrallah H, Luchins D, Bigelow L, Linnoila M, Fischer SH, Bjornsson TD, Carman J, Gillin JC, Wyatt RJ. Am J Psychiatry 1981 Sep;138(9):1208-11

Gamma-Linolenic acid: Reportedly has had modest therapeutic effect. Also dihomo=GLA. Impaired prostaglandin metab in schiz and abn EFA biochem. Prostaglandins Leukot Essent Fatty Acids 5/92 46:71-7. Low linoleic acid and elevated 22-C EFAs of both n-6 and n-3 in schiz.

Gingko Helps Schiz: 545 pt DB PC add-on 1 wk study of shuxuening, an extract of gingko, at 120 mg TID. 45% major improvement with Gingko vs. 21% on Global Improvement. Gingko better for BPRS and for negative symptom scale, too. Anti-psychotics were continued during the study. Effect significant as of 6 weeks. HC Luo, Beijing Med Univ, Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 3/97;17(3):139

Haldol: 4 mg/day Enough: A DB study found no added benefit to higher doses of 10 mg or 40 mg/day. Stone, University of Texas, Am J Psychiatry ’95;152:1210

Haldol Decanoate 200 mg/mo Best; Use at Least 50 mg/mo: In a DB random assignment study of 105 patients, rates of symptomatic exacerbation were 15% in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg, however, differences between 50, 100, and 200 were not significant. Am J Psychiatry 2002 Apr;159(4):554-60

Haldol did as Well as Olanzapine in Large DB: A 309-patient 1-year VA study of schizophrenic patients with serious symptoms and dysfunction for the previous two years randomized to  haloperidol 5-20 mg/d and prophylactic benztropine mesylate 1-4 mg daily, olanzapine 5-20 mg/d and benztropine placebo. 59% completed the study, while 39% partially completed the year-long assessment period. There were no significant differences between the olanzapine group and the haloperidol group in completion rates (45.9% vs. 39.3%; P = .25), nor in reasons for discontinuation. Comparable scores on the Positive and Negative Syndrome Scale (PANSS) over 12 months, both on total score (P = .35), and positive and negative subscales (P = .64 and P = 0.31, respectively). The haloperidol cohort did achieve higher scores on the Heinrichs-Carpenter Quality of Life Scale (QOLS), but only at six weeks (P = .04), and overall there were no significant differences between the groups (P = .71). Olanzapine had lower scores for akathesia, but not for tardive dyskinesia or other extrapyrimidal symptoms. Weight gain was much more frequently reported with olanzapine group. Although no significant differences in costs for VA service, olanzapine medication costs were four to five times higher, resulting in a $3,000 to $9,000 increase in total annual health costs. Robert Rosenheck, JAMA. 11/26/2003;290:2693-2702. (Ed: Psychiatrists in the U.S. have almost totally abandoned traditional anti-psychotics under the promotion that atypicals led by olanzapine work so much better with so many fewer side-effects.  Yet, this is the largest long-term study ever done.) For more, see Olanzapine. 

Haldol: Anti-psychotics, Especially Haldol Have Higher Rate of Sudden Death: 250,000 Dutch patients from 1995-2001 experience 582 cases of sudden cardiac death or 1 per 1000 person-years per year. Current use of antipsychotics was associated with a threefold risk increase (OR, 3.3) but not past use. Risk was highest for haloperidol. The risk increased significantly with higher doses (P < .001). For current users (OR, 4.7 compared with 2.4); men vs. women (OR, 4.9 vs. 2.9); those younger than 65 years (OR, 5.5 vs. 3.1 for those older than 65 years). Sabine M.J. M. Straus, Erasmus University, Rotterdam. Arch Intern Med. 6/28/2004;164:1293-1297

Histamine H2 Receptor Antagonists: Famotidine Used in Open Trial: 18 patients acute exacerbation schiz or schizoaffective with average 17 yr hx and 140 days in hosp in previous two years. Added to conventional neuroleptics at high dose of 100 mg/d for 3 weeks. Reported 16% improvement, but seems a worthless study that proves nothing. Rosse R el al, An open-label study of the therapeutic efficacy of high dose famotidine adjuvant pharmacotherapy in schizophrenia: preliminary evidence for treatment efficacy. Clin Neuroph 96;19:341-8, Wash DC VA. Says previous reports of benefit at 40mg/d.

Lamotrigine May Help: A small 34-patient DB PC study of schizophrenic patients on clozapine and gradually increased to 200 mg/d of lamotrigine in addition found lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms. U Helsinki. Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Tiihonen J, Hallikainen T, et al. Biol Psychiatry. 2003 Dec 1;54(11):1241-8

L-Tyrosine: No Help in DB: 3 weeks DB PC 10g/d. Clin Neuropharmacol. 1994 Feb;17(1):53-62. L-tyrosine pharmacotherapy of schizophrenia: preliminary data. Deutsch SI, Rosse RB, Schwartz BL, Banay-Schwartz M, McCarthy MF, Johri SK.

Mianserin: Addition to Typicals May Help 5HT2 serotonergic Blockade: 30 mg/day mianserin (n = 9) or placebo (n = 9) with typical neuroleptics [haloperidol or perphenazine]. DB 6 weeks of combined treatment with BPRS, Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group significantly greater improvement in BPRS (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). chronic treatment-resistant schizophrenia with acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. emphasize the contribution of enhanced 5-HT2 blockade of the atypicals. Int Clin Psychopharmacol 2002 Mar;17(2):59-64

Modafinil No Benefit and May Aggravate Psychosis: In a DB PC 8-week study of 24 patients with schizophrnia, modafinil up to 200 mg a day was no better than placebo for fatigue, positive and negative symptoms, or cognition. Fatigue was reduced in both groups. One modafinil patient dropped out due to a worsening of psychosis. Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications. Sevy S, et al. Zucker Hillside Hospital,  Glen Oaks, N.Y. J Clin Psychiatry. 2005 Jul;66(7):839-43

Naltrexone No Benefit: DB PC crossover 3 week 200mg/d add-on study 21 pt. Sernyak, Yale, J Clin Psychopharm ’98;18:248

Leukopenia Rx with Olanzapine Dosage Decrease: Three cases neutropenia. Two had had agranulocytosis on conventional neuroleptics (sic). Neutropenia resolved in all three cases with decrease of dose to 5mg/d. Israel, Int Clin Psychoph 01;16:117

rTMS: Auditory Hallucinations Helped by L temporoparietal rTMS: Neuroimaging studies suggest that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. One-hertz rTMS produces sustained reductions in cortical activation. 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs. More extended trial of rTMS significantly reduces AHs that are resistant to antipsychotic medication. 24 patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. Auditory hallucinations were robustly improved with rTMS relative to sham stimulation. Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks. Repetitive transcranial magnetic stimulation was well tolerated. Yale. Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations. Hoffman RE, Hawkins KA, Gueorguieva R, Boutros NN, Rachid F, Carroll K, Krystal JH. Arch Gen Psychiatry 2003 Jan;60(1):49-56

rTMS: Right Prefrontal rTMS No Benefit in DB: 35 schiz pt. 2weeks rx. DB with sham control. Right prefrontal slow repetitive transcranial magnetic stimulation in schizophrenia: a double-blind sham-controlled pilot study. Klein E, Kolsky Y, Puyerovsky M, Koren D, Chistyakov A, Feinsod M. Biol Psychiatry 1999 Nov 15;46(10):1451-4, Haifa

Sertindole: As Good As Haldol: DB 497 pt 4, 8, 16 mg/d vs haldol. Loma Linda, Am J Psych ’97;154:782

Sertraline No Effect: DB PC add-on to Haldol found no change in pos or neg symptoms in 8 wk study or in EPS. Lee, Korea Univ, J Clin Psychopharm 10/98;18:399

Sertraline = Imipramine for Post-Psychotic Depr: DB Sert 50mg/d vs Imip 150mg/d 4 weeks. No difference in benefit to depr tho Sert acted more quickly and with fewer side-effects. Kurli, Turkey, Schiz Res 9’98;33:103

Thioridazine: Higher Sudden Death: Sudden death odds ratio 5.0 compared to other state hosp matched patients. Regulatory agencies recommend restrict to refractory schiz. Br J Psych 02;180:515

Thiothixene Alone = Chlorpromazine + Imipramine: DB PC 4 week 52 depressed, anergic schizophrenics. No difference. Confirms wisdom of just using an anti-psychotic. Implications of the efficacy of thiothixene and a chlorpromazine-imipramine combination for depression in schizophrenia. Becker RE. Am J Psychiatry 1983 Feb;140(2):208-11

Topiramate Used as Add-On: Unclear Results: In a 12-week each DB PC crossover study of 26 hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia, while on 300 mg/day of topiramate added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) they had "a reduction in the Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms." Topiramate Add-On in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. Tiihonen J, et al. University of Kuopio, Finland. J Clin Psychiatry. 2005 Aug;66(8):1012-1015. Ed: If you understand what they said, please let me know.

Tyrosine: No Added Benefit: DB PC 3 wk, 10g/d. Deutsch, VA, Clin Neuropharm ’94;17:53

Valacyclovir Helped Schizophrenic Patients Positive for Cytomegalovirus: A study of 65 out-patients treated for 16 weeks with 1 g/d of valacyclovir found a significant decrease in positive and negative symptom scores on the PANSS test only in patients positive for cytomegalovirus and not for patients sero-positive for other herpes viruses. The authors conclude that the replication of cytomegalovirus may play a role in some schizophrenia. Johns Hopkins. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia. Dickerson FB, Boronow JJ, Stallings CR, Origoni AE, Yolken RH. Am J Psychiatry. 2003 Dec;160(12):2234-6; 

    The CDC says cytomegalovirus infects between 50% and 85% of adults in the United States by 40 years of age. CMV is also the virus most frequently transmitted to a developing child before birth. For most healthy persons who acquire CMV after birth there are few symptoms and no long-term health consequences. Some persons with symptoms experience a mononucleosis-like syndrome with prolonged fever, and a mild hepatitis. Once a person becomes infected, the virus remains alive, but usually dormant within that person's body for life. Recurrent disease rarely occurs unless the person's immune system is suppressed due to therapeutic drugs or disease. Infectious CMV may be shed in the bodily fluids of any previously infected person, and thus may be found in urine, saliva, blood, tears, semen, and breast milk. The shedding of virus may take place intermittently, without any detectable signs, and without causing symptoms. It may be sexually transmitted. 

    Risks to newborns appear to be almost exclusively associated with pregnant women who previously have not been infected with CMV and who are having their first infection with the virus during pregnancy. Even in this case, two-thirds of the infants will not become infected, and only 10-15% of the remaining third will have symptoms at the time of birth. There appears to be little risk of CMV-related complications for women who have been infected at least 6 months prior to conception. For this group, which makes up 50% to 80% of the women of child-bearing age, the rate of newborn CMV infection is 1%, and these infants appear to have no significant illness or abnormalities.

    The virus can also be transmitted to the infant at delivery from contact with genital secretions or later in infancy through breast milk. However, these infections usually result in little or no clinical illness in the infant.

Valproate: Divalproex (Depakote) Helps as Adjunct: In a 21-day DB PC study of just 12 patients ages 21-41, all were treated with haloperidol 10 mg/day for 3 days and then 15 mg/d. Just five were given divalproex up to 75 microg/ml. Divalproex patients reportedly did significantly better. 3 placebo patients improved markedly with addition of dival. Wassef, J Clin Psychoph 00;20:357. Ed: Significant findings from such an extremely small study are hard to put much confidence in.

Valproate: Divalproex Adjunct Increased Speed of Recovery But Not Amount: 248 schiz DB risperidone 2mg/d to 6mg on 6th day, olanzapine 5/d to 15 on 6th , risperidone + divalproex 15mg/kg/d raised to 30/kg/d, olanzapine + same divalproex. Faster recovery noted by 3rd day. Benefit noted on PANSS but not BPRS. Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Casey DE, Daniel DG, Wassef AA, Tracy KA, Wozniak P, Sommerville KW. Neuropsychopharmacology 2003 Jan;28(1):182-92. Ed: probably industry funded. Faster recovery with faster med loading.

Valproate No Added Benefit: DB PC found increased EPS with Valproate and some decrease in overall belligerence but no overall benefit. Dose, Germany, Psychopharm ’98;31:122

Thomas E. Radecki, M.D., J.D.

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