Procaine treatments for cognition and dementia

Szabolcs Szatmári; Dániel Bereczki

doi:10.1002/14651858.CD005993.pub2

Tratamientos con procaína para la cognición y la demencia

Contraer todo Desplegar todo

Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

estudios excluidos
otras referencias

Balaceanu Stolnici C, Manoiu A, Vrabiescu M. Gerovital h3 effects upon human cognitive behaviour and psychomotor capacity. Romanian Journal of Gerontology and Geriatrics 1989;10(4):277‐84.

Google Scholar

Cashman MD, Lawes TGG. A controlled trial of "Gerioptil". BMJ 1961;1(5225):554‐6.

Hall MR, Briggs RS, MacLennan WJ, Marcer D, Robinson MJ, Everett FM. The effects of procaine/haematoporphyrin on age‐related decline: a double‐blind trial. Age and Ageing 1983;12(4):302‐8.

The Southampton Ageing Project. The Southampton Ageing Project: A trial of KH3. The Southampton Ageing Project1982.

Referencias de los estudios excluidos de esta revisión

Ir a:

estudios incluidos
otras referencias

Abrams A, Tobin S, Gordon P, Pechtel C, Hilkevitch A. The effects of a European procaine preparation in an aged population. Journal of Gerontology 1965;20(2):139‐43.

Aslan A. A new method for prophylaxis and treatment of aging with novocain‐eutrophic and rejuvenating effects. Therapiewoche 1956;7:14‐22.

Google Scholar

Aslan A, Vrabiescu A, Dobre M. Aslavital for children in mentally deficient subjects. Romanian Journal of Gerontology and Geriatrics 1980;1(2):189‐94.

Google Scholar

Aslan A, Vrabiescu A, Dobre M, Polovrageanu E. The aslavital treatment in the recovery of mentally‐deficient children. Romanian Journal of Gerontology and Geriatrics 1980;1(1):93‐8.

Google Scholar

Berryman JAW, Forbes HAW, Simpson‐White R. Trial of procaine in old age and chronic degenerative disorders. BMJ 1961;2(5268):1683‐4.

Czerwenka H, Maly J, Quatember R, Tschabitscher H. Clinical and psychological investigations with a geriatric substance (in German) [Klinische und testpsychologische Untersuchungen mit einem Geriatricum]. Wiener Medizinische Wochenschrift 1970;120(13):217‐24.

Fee SR, Clark ANG. Trial of procaine in the aged. BMJ 1961;2(5268):1680‐2.

Gericke OL, Lobbv LG, Pardoll DH. An evaluation of procaine in geriatric patients in a mental hospital. Journal of Clinical and Experimental Psychopathology 1961;22:18‐33.

Google Scholar

Hirsch J. A clinical trial of procaine hydrochloride. BMJ 1961;2(5268):1684‐5.

Isaacs B. Trials of procaine in aged patients. BMJ 1962;2(5272):188‐9.

Kant S, Sterne DM. Evaluation of chronically ill patients treated for one year with procaine. Journal of the American Geriatrics Society 1962;10:408‐12.

Kent S. The procaine "youth" drugs. Geriatrics 1982;37(4):32‐6.

Long RF, Gislason SS. The effect of procaine on orientation, attention, memory and weight of aged psychiatric patients. Journal of Neuropsychiatry 1964;5:186‐96.

May RH, Ruland MB, Bylenga ND, Peppel HH. Prolonged procaine therapy in geriatric psychiatric patients. Geriatrics 1962;17:161‐8.

Olsen EJ, Bank L, Jarvik LF. Gerovital‐H3: a clinical trial as an antidepressant. Journal of Gerontology 1978;33(4):514‐20.

Ostfeld A, Smith CM, Stotsky BA. The systemic use of procaine in the treatment of the elderly: a review. Journal of the American Geriatrics Society 1977;5(1):1‐19.

Quatember R, Maly J. Neuropsychological methods of examination of age‐specific performance parameters [Neuropsychologische Untersuchungsmethoden alterssezifischer Leistungsparameter]. Wiener Medizinische Wochenschrift 1980;130(21):688‐92.

Rusu C, Borsa C, Gradinaru D, Ionescu C, Babeanu S. Antioxidant and lipid‐lowering effects of the original procaine‐based products. Romanian Journal of Gerontology and Geriatrics 1996;18(3‐4):47‐61.

Google Scholar

Sakalis G, Oh D, Gershon S, Shopsin B. A trial of gerovital H‐3 in depression during senility. Current Therapeutic Research, Clinical and Experimental 1974;16(1):59‐63.

Smigel JO, Piller J, Murphy C, Lowe C, Gibson J. H‐3 (procaine hydrochloride) therapy in aging institutionalized patients: an interim report. Journal of the American Geriatrics Society 1960;8:785‐94.

Valtonen EJ. Procaine chloride as a universal remedy for somatic and psychic symptoms. Suomen Lookorilehti 1992;47(28):1608‐11.

Google Scholar

Zdichynec B. Successes in novocain therapy in the control of premature ageing [Kurzmitteilung zur Novokaintherapie‐Vorbeugung des vorzeitigen Alterns mittels der Novokaintherapie]. Z Alternsforsch 1977;32(3):267‐9.

Zwerling I, Plutchik R, Hotz M, Kling R, Rubin L, Grossman J, et al. Effects of a procaine preparation (Gerovital H3) in hospitalized geriatric patients: a double‐blind study. Journal of the American Geriatrics Society 1975;23(8):355‐9.

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd Edition. Washington, DC: American Psychiatric Association, 1987.

American Psychiartric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association. Vol IV. IV. Washington, DC, USA: American Psychiatric Publishing, 1994.

Automatic detention alert for Gerovital. http://www.fda.gov/ora/fiars/ora_import_ia6101.html.

http://www.gh3.co.uk/.

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 5.0.0 [updated February 2008]. Available from www.cochrane‐handbook.org. The Cochrane Collaboration.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical Diagnosis of Alzheimer's Disease: Report of the NINCDS‐ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;4:939‐44.

Román CG, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS‐AIREN International Workshop. Neurology 1993;43:250‐60.

Development of Ultimate 9. http://www.achilleshealthmart.com/vitacel_koch.htm.

World Health Organisation. International classification of diseases, 10th revision. Geneva: World Health Organisation, 1992.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

Balaceanu 1989

Methods	Double‐blind, placebo‐controlled, randomized, method of randomization not detailed.
Participants	Aging persons free of neuropsychiatric pathology from the Romanian National Institute of Gerontology and Geriatrics. Procaine group: 41 patients (25 women and 16 men), mean age: 71.9 years. Placebo group: 40 patients (28 women and 12 men), mean age: 71.3 years.
Interventions	Gerovital H3 or saline solution 2 x 5 ml per day i.m. during 30 days
Outcomes	Psychomotor capacity, Herwig's attention test, Wechsler's Memory scale, Kohs cubes intelligence test
Notes	No details about extracerebral diseases. Adverse effects reported.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not detailed
Allocation concealment?	Unclear risk	Unclear
Blinding? All outcomes	Unclear risk	Not detailed
Incomplete outcome data addressed? All outcomes	Low risk
Free of selective reporting?	Low risk
Free of other bias?	Unclear risk	The study was too short, no data about follow up

Cashman 1961

Methods	Double‐blind, placebo‐controlled, randomized, method of randomization not detailed.
Participants	Moderate or advanced senile or arterioslerotic dementia. 12 elderly women, 6 active (between 64 and 81 years old) and 6 placebo (between 76 and 84 years old)
Interventions	gerioptil or placebo, a number of 12 injections i.m. during 1 month
Outcomes	Wechsler's memory test Bender gestalt test of figure‐drawing Raven's Progressive Matrices Mill Hill vocabulary test
Notes	No criteria for dementia. Adverse events not mentioned
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not detailed
Allocation concealment?	Unclear risk	Unclear
Blinding? All outcomes	Unclear risk	Not sufficiently detailed
Incomplete outcome data addressed? All outcomes	Low risk
Free of selective reporting?	Low risk
Free of other bias?	Unclear risk	Short study with small number of patients, no follow up

Hall 1983

Methods	Double‐blind, placebo‐controlled, randomized, method of randomization not detailed.
Participants	So‐called "healthy elderly, fit enough to go through tests" 168 active and 166 placebo, all over 65 years old Mean age of completers on entry: active: 72.8 (5.3) years (standard deviation); placebo: 73.7 (6.3) exclusion criteria: severe diseases
Interventions	KH3 (procaine/haematoporphyrin) or placebo 1 x 50 mg/day per os for 2 years
Outcomes	Recall and recognition of familiar material Immediate free recall Digit span Wechsler Adult Intelligence Scale (comprehension, vocabulary) Raven's Progressive Matrices
Notes	There were clinical and laboratory abnormalities at screening and baseline: electrocardiographic abnormalities 45%, blood haemoglobin concentration of less than 12 g/dl in 6% and history of stroke: 4%, angina or intermittent claudication: 16%. Dropouts: 87 subjects, 49 for active (withdrawals without side effects: 18, withdrawals for side effects: 13, death: 18), 38 for placebo (withdrawals without side‐effects: 17, withdrawals for side effects: 2, death: 19)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Insufficiently detailed
Allocation concealment?	Unclear risk	Unclear
Blinding? All outcomes	Unclear risk	Insufficiently detailed
Incomplete outcome data addressed? All outcomes	Low risk
Free of selective reporting?	Unclear risk	Only side effects causing withdrawals were reported
Free of other bias?	Low risk

Southampton 1982

Methods	Same study as Hall 1983, this is the detailed unpublished report of the trial Double‐blind, placebo‐controlled, randomized, method of randomization not detailed.
Participants	So‐called "healthy elderly, fit enough to go through tests" 168 active and 166 placebo, all over 65 years old Mean age of completers on entry: active: 72.8 (5.3) years (standard deviation); placebo: 73.7 (6.3) Exclusion criteria: severe diseases
Interventions	KH3 (procaine/haematoporphyrin) or placebo 1 x 50 mg/day for 2 years
Outcomes	Recall and recognition of familiar material Immediate free recall Digit span Wechsler Adult Intelligence Scale (comprehension, vocabulary) Raven's Progressive Matrices
Notes	There were clinical and laboratory abnormalities at screening and baseline: electrocardiographic abnormalities 45%, blood haemoglobin concentration of less than 12 g/dl in 6% and history of stroke: 4%, angina or intermittent claudication: 16%. Dropouts: 87 subjects, 49 for active (withdrawals without side effects: 18, withdrawals for side effects: 13, death: 18), 38 for placebo (withdrawals without side effects: 17, withdrawals for side effects: 2, death: 19)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Insufficiently detailed
Allocation concealment?	Unclear risk	Unclear
Blinding? All outcomes	Unclear risk	Insufficiently detailed
Incomplete outcome data addressed? All outcomes	Low risk
Free of selective reporting?	Unclear risk	Only side effects causing withdrawals were reported
Free of other bias?	Low risk

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Abrams 1965	Randomized, double blind study comparing two procaine preparations. The study evaluates the effects of the additives and not of procaine.
Aslan 1980	Double blind, placebo controlled study performed in children with mental deficiency.
Berryman 1961	RCT but heterogenous groups with diverse diseases (cerebral haemorrhage, cerebral arteriosclerosis, Parkinsonism, rheumatoid arthritis, diabetes mellitus, old breast carcinoma, senile dementia), subgroup analysis not possible. Not healthy, not only demented subjects.
Czerwenka 1970	Not randomized, double blind, placebo controlled study
Fee 1961	Double blind, placebo controlled trial including physically infirm residents in an elderly home. Cognitive functions not tested.
Gericke 1961	Not RCT, elderly hospitalized patients with a history of arteriosclerosis or degenerative arthritis.
Hirsch 1961	Randomized, double blind, placebo controlled trial but heterogeneous groups with diverse diseases (cerebral thrombosis, Parkinson's disease, pseudobulbar palsy, senile dementia, rheumatoid arthritis, congestive cardiac failure etc.). Cognitive functions not tested.
Isaacs 1962	Not RCT, patients with diverse diseases, cognitive functions not tested.
Kant 1962	Randomized, double blind, placebo controlled trial but heterogeneous group with diverse, multiple diseases (arteriosclerotic heart disease, peripheral arteriosclerosis obliterans, residuals of cerebrovascular accidents, peptic ulcer, osteoarthritis, emphysema, visual and auditory impairment, intellectual deterioration). Subgroup analysis was not possible.
Kent 1982	Review of procaine studies
Long 1964	Randomized, double blind, placebo controlled trial, including heterogeneous groups of disoriented psychiatric patients. No criteria for cognitive impairment or dementia. There was a 45% loss of patients from follow up during the study.
May 1962	Not randomized, double blind, placebo controlled study on white, female, geriatric, psychiatric patients. Evaluation of cognitive functions not detailed.
Olsen 1978	RCT, but patient population is of depression, no cognitive tests.
Ostfeld 1977	Review of procaine studies
Quatember 1980	Not randomized, double blind, placebo controlled study
Rusu 1996	Not randomized, not double blind, controlled study for lipid‐lowering effects
Sakalis 1974	Open study for depression in elderly
Smigel 1960	Double blind, placebo controlled study, randomization by alternation (category C, inadequate), heterogeneous group of geriatric patients with "arthritis, nervous disorders and senile mental disturbances"
Valtonen 1992	RCT, healthy volunteers, subjective assessment of 36 symptoms, cognitive functions not tested.
Zdichynec 1977	Not randomized, double blind, placebo controlled study on arteriosclerotic cardiovascular and cerebrovascular patients
Zwerling 1975	Not randomized, double blind, placebo controlled, small study in hospitalized geriatric patients with organic brain dysfunction

Data and analyses

Open in table viewer

Comparison 1. Procaine 200 mg/day i.m. during 30 days vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 attention, Herwig's test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 1 attention, Herwig's test (change from baseline).
1.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	1.59 [0.64, 3.95]
2 information, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.2 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 2 information, Wechsler's Memory Scale (change from baseline).
2.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	5.13 [0.24, 110.20]
3 orientation, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 3 orientation, Wechsler's Memory Scale (change from baseline).
3.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	3.0 [0.12, 75.85]
4 mental control, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 4 mental control, Wechsler's Memory Scale (change from baseline).
4.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.74 [2.31, 33.05]
5 immediate logic recall, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 5 immediate logic recall, Wechsler's Memory Scale (change from baseline).
5.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	2.40 [0.98, 5.93]
6 digit memory, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.6 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 6 digit memory, Wechsler's Memory Scale (change from baseline).
6.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	18.11 [2.24, 146.55]
7 visual memory, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 7 visual memory, Wechsler's Memory Scale (change from baseline).
7.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	10.97 [1.32, 91.22]
8 associate learning, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 8 associate learning, Wechsler's Memory Scale (change from baseline).
8.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	12.95 [3.44, 48.79]
9 memory quotient, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 9 memory quotient, Wechsler's Memory Scale (change from baseline).
9.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	12.71 [3.81, 42.42]
10 intelligence ‐ Kohs cubes test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.10 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 10 intelligence ‐ Kohs cubes test (change from baseline).
10.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.31, 3.07]
11 number of patients with at least one adverse event during procaine 10 ml/day after 30 days Show forest plot	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]
Open in figure viewer Analysis 1.11 Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 11 number of patients with at least one adverse event during procaine 10 ml/day after 30 days.
11.1 number of patients with at least one adverse event during procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]

Open in table viewer

Comparison 2. Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 withdrawals during the treatment with procaine/hematoporphyrin 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 1 withdrawals during the treatment with procaine/hematoporphyrin 50 mg/day 2 years.
1.1 procaine/hematoporphyrin 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	1.78 [0.96, 3.29]
2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years.
2.1 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	6.96 [1.55, 31.36]
3 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.3 Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 3 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years.
3.1 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.48, 1.86]

Open in table viewer

Comparison 3. Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 memory quotient, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.1 Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 1 memory quotient, Wechsler's Memory Scale (change from baseline).
1.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 1.12]
2 figure‐drawing, Bender gestalt test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.2 Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 2 figure‐drawing, Bender gestalt test (change from baseline).
2.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.15]
3 intellectual capacity, Raven's Progressive Matrices (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.3 Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 3 intellectual capacity, Raven's Progressive Matrices (change from baseline).
3.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.15]
4 premorbid intelligence level, Mill Hill vocabulary scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.4 Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 4 premorbid intelligence level, Mill Hill vocabulary scale (change from baseline).
4.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.02, 2.76]
5 overall changes from baseline Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.5 Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 5 overall changes from baseline.
5.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 0.83]

Open in table viewer

Comparison 4. Procaine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 total adverse events Show forest plot	2	415	Odds Ratio (M‐H, Fixed, 95% CI)	7.30 [2.13, 25.02]
Open in figure viewer Analysis 4.1 Comparison 4 Procaine vs placebo, Outcome 1 total adverse events.
1.1 number of patients with at least one adverse event during procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]
1.2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	6.96 [1.55, 31.36]

Analysis 1.1

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 1 attention, Herwig's test (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 2 information, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 3 orientation, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 4 mental control, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 5 immediate logic recall, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 6 digit memory, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 7 visual memory, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 8 associate learning, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 9 memory quotient, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.10

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 10 intelligence ‐ Kohs cubes test (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.11

Comparison 1 Procaine 200 mg/day i.m. during 30 days vs placebo, Outcome 11 number of patients with at least one adverse event during procaine 10 ml/day after 30 days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 1 withdrawals during the treatment with procaine/hematoporphyrin 50 mg/day 2 years.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo, Outcome 3 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 1 memory quotient, Wechsler's Memory Scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 2 figure‐drawing, Bender gestalt test (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.3

Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 3 intellectual capacity, Raven's Progressive Matrices (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.4

Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 4 premorbid intelligence level, Mill Hill vocabulary scale (change from baseline).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.5

Comparison 3 Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo, Outcome 5 overall changes from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 Procaine vs placebo, Outcome 1 total adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. procaine compared to placebo for cognitive enhancement and dementia

procaine compared to placebo for cognitive enhancement and dementia
Patient or population: "healthy" old persons and demented women Settings: Intervention: procaine ¹
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	procaine
cognitive function improvement in "healthy" elderly persons Wechsler's memory scale² Follow‐up: 30 days	Medium risk population		OR 12.71 (3.81 to 42.42)	81 (1 study)	⊕⊕⊝⊝ low^3,4,5
	100 per 1000	585 per 1000 (297 to 825)
cognitive function improvement in demented women Wechsler's memory scale² Follow‐up: 30 days	Medium risk population		OR 0.04 (0 to 1.12)	12 (1 study)	⊕⊝⊝⊝ very low^3,5,6
	667 per 1000	74 per 1000 (0 to 692)
overall changes from baseline in "healthy persons⁷ ‐ not measured	See comment	See comment	Not estimable⁷	‐	See comment
overall changes from baseline in demented women Follow‐up: 30 days	Medium risk population		OR 0.04 (0 to 0.83)	12 (1 study)	⊕⊝⊝⊝ very low^3,5,6
	833 per 1000	166 per 1000 (0 to 805)
total adverse events in "healthy" persons Follow‐up: 30 days to 2 years	Low risk population⁸		OR 7.3 (2.13 to 25.02)	415 (2 studies)	⊕⊕⊝⊝ low^3,4,9
	10 per 1000	69 per 1000 (21 to 202)
	High risk population⁸
	20 per 1000	130 per 1000 (42 to 338)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ procaine was used for 30 days in two studies and for 2 years in one other study ² memory quotient rated as improved ‐ not improved related to the baseline ³ randomisation not detailed ⁴ not really "healthy" subjects ⁵ short trial without follow up ⁶ small number of patients ⁷ no data about overall changes ⁸ different length of two trials and different way of administration: i.m. and per os ⁹ one trial was very short without follow up and one trial reported only side effects causing withdrawals

Summary of findings for the main comparison. procaine compared to placebo for cognitive enhancement and dementia

Ir a la tabla de la revisión

Comparison 1. Procaine 200 mg/day i.m. during 30 days vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 attention, Herwig's test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	1.59 [0.64, 3.95]
2 information, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	5.13 [0.24, 110.20]
3 orientation, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	3.0 [0.12, 75.85]
4 mental control, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.74 [2.31, 33.05]
5 immediate logic recall, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	2.40 [0.98, 5.93]
6 digit memory, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	18.11 [2.24, 146.55]
7 visual memory, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	10.97 [1.32, 91.22]
8 associate learning, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	12.95 [3.44, 48.79]
9 memory quotient, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	12.71 [3.81, 42.42]
10 intelligence ‐ Kohs cubes test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.31, 3.07]
11 number of patients with at least one adverse event during procaine 10 ml/day after 30 days Show forest plot	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]

11.1 number of patients with at least one adverse event during procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]

Comparison 1. Procaine 200 mg/day i.m. during 30 days vs placebo

Ir a la tabla de la revisión

Comparison 2. Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 withdrawals during the treatment with procaine/hematoporphyrin 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 procaine/hematoporphyrin 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	1.78 [0.96, 3.29]
2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	6.96 [1.55, 31.36]
3 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 death during the treatment with procaine/hematoporphyrin 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.48, 1.86]

Comparison 2. Procaine/hematoporphyrin (KH3) 50 mg/day per os during 2 years vs placebo

Ir a la tabla de la revisión

Comparison 3. Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 memory quotient, Wechsler's Memory Scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 1.12]
2 figure‐drawing, Bender gestalt test (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.15]
3 intellectual capacity, Raven's Progressive Matrices (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.15]
4 premorbid intelligence level, Mill Hill vocabulary scale (change from baseline) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.02, 2.76]
5 overall changes from baseline Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 gerioptil H3 12 injections/1 month	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 0.83]

Comparison 3. Procaine (gerioptil H3) 12 injections/1 month i.m. vs placebo

Ir a la tabla de la revisión

Comparison 4. Procaine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 total adverse events Show forest plot	2	415	Odds Ratio (M‐H, Fixed, 95% CI)	7.30 [2.13, 25.02]

1.1 number of patients with at least one adverse event during procaine 10 ml/day after 30 days	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	8.03 [0.94, 68.60]
1.2 withdrawals due to adverse event during the treatment with procaine (KH3) 50 mg/day 2 years	1	334	Odds Ratio (M‐H, Fixed, 95% CI)	6.96 [1.55, 31.36]

Comparison 4. Procaine vs placebo

Ir a la tabla de la revisión

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Referencias

Referencias de los estudios incluidos en esta revisión

Balaceanu 1989 {published data only}

Cashman 1961 {published data only}

Hall 1983 {published and unpublished data}

Southampton 1982 {unpublished data only}

Referencias de los estudios excluidos de esta revisión

Abrams 1965 {published data only}

Aslan 1980 {published data only}

Berryman 1961 {published data only}

Czerwenka 1970 {published data only}

Fee 1961 {published data only}

Gericke 1961 {published data only}

Hirsch 1961 {published data only}

Isaacs 1962 {published data only}

Kant 1962 {published data only}

Kent 1982 {published data only}

Long 1964 {published data only}

May 1962 {published data only}

Olsen 1978 {published data only}

Ostfeld 1977 {published data only}

Quatember 1980 {published data only}

Rusu 1996 {published data only}

Sakalis 1974 {published data only}

Smigel 1960 {published data only}

Valtonen 1992 {published data only}

Zdichynec 1977 {published data only}

Zwerling 1975 {published data only}

Referencias adicionales

APA 1987

DSM IV 1994

FDA 1982

GH3 2008

Higgins 2008

McKhann 1984

Román 1993

Ultimate 9 2008

WHO 1992

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

Copiar o descargar referencia

Idioma de la Revisión Cochrane

Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso