Compatibility between Cochrane Database systematic reviews categorised as pharmacological to the most recent APA guidelines’ treatment recommendations
| Cochrane publication | Drug | Cochrane recommendation | APA recommendation | Congruence between APA and Cochrane |
| Leucht S, Helfer B, Dold M, et al. Lithium for schizophrenia. Cochrane Database Syst Rev 2015;:CD003834. | Lithium | There is currently no evidence from randomised controlled trials to support the use of lithium alone as treatment for people with schizophrenia | Lithium as a sole treatment has limited effectiveness in schizophrenia and is inferior to treatment with antipsychotic medications | + |
| Sampson S, Hosalli P, Furtado VA, et al. Risperidone (depot) for schizophrenia. Cochrane Database Syst Rev 2016;4:CD004161. | Risperidone | Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders | Depot injections should be considered in patients with resistance to treatment | 0 |
| Li C, Xia J, Wang J. Risperidone dose for schizophrenia. Cochrane Database Syst Rev 2009;:CD007474. | Risperidone | There is still lack of strong evidence for an optimal dose for clinical practice | There is still a lack of evidence for most efficacious dose of risperidone for schizophrenic patients | + |
| Komossa K, Rummel-Kluge C, Hunger H, et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009;:CD006627. | Ziprasidone | Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings | There are several published clinical trials comparing the efficacy of ziprasidone with placebo and with first-generation antipsychotics in the acute treatment of patients with schizophrenia, schizoaffective disorder and schizophreniform disorder. Placebo-controlled studies consistently demonstrate that in acutely relapsed patient’s ziprasidone is efficacious in the treatment of global psychopathology and the positive symptoms of schizophrenia, as well as in increasing the likelihood of clinical response (eg, ≥20% improvement on rating scales of global psychopathology) | 0 |
| Rattehalli RD, Zhao S, Li BG, et al. Risperidone versus placebo for schizophrenia. Cochrane Database Syst Rev 2016;12:CD006918. | Risperidone | Based on low-quality evidence, risperidone appears to be beneficial in improving mental state compared with placebo, but it also causes more adverse events | There are numerous published clinical trials comparing the acute efficacy of risperidone with placebo, first-generation antipsychotics (haloperidol or perphenazine) and other second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder, and schizophreniform disorder. Placebo-controlled studies consistently demonstrate that for acutely relapsed patients, risperidone is efficacious in the treatment of global psychopathology and the positive symptoms of schizophrenia (886–888), as well as in increasing the likelihood of clinical response (eg, ≥20% improvement on rating scales of global psychopathology) | 0 |
| Komossa K, Rummel-Kluge C, Hunger H, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010;:CD006654. | Olanzapine | Olanzapine may be a somewhat more efficacious drug than some other second-generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second-generation antipsychotic drugs, except clozapine | Studies comparing olanzapine to other second-generation antipsychotics in the treatment of acute episodes have generally found similar efficacy for treatment of psychopathology both in patients with treatment-responsive symptoms and in those with treatment-resistant symptoms (381, 820, 905, 906), with some exceptions in which olanzapine was found to be superior (820, 902) | + |
| Asenjo Lobos C, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010;:CD006633. | Clozapine | Clozapine may be a little more efficacious than zotepine and risperidone, but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second-generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient’s preferences | In addition, studies comparing clozapine to other second-generation antipsychotics generally show comparable efficacy of clozapine with other second-generation antipsychotics (87, 381, 820, 848). However, since relatively low doses of clozapine were used in these studies, the results must be interpreted with caution | 0 |
| Komossa K, Rummel-Kluge C, Schwarz S, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2011;:CD006626. | Risperidone | Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other SGAs. It may also differ from other compounds in efficacy and in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions | Studies comparing risperidone to other second-generation antipsychotics in the treatment of acute episodes have generally found similar efficacy for treatment of psychopathology both in patients with treatment-responsive illness and in those with treatment-resistant illness (848, 902, 905–907). Table 4 of the guideline addresses the side effect profile of risperidone | 0 |
| Belgamwar RB, El-Sayeh HGG. Aripiprazole versus placebo for schizophrenia. Cochrane Database Syst Rev 2011;:CD006622. | Aripiprazole | Aripiprazole may be effective for the treatment of schizophrenia. Aripiprazole has a lower risk of raised prolactin and prolongation of the QTc interval | Placebo-controlled studies consistently demonstrate that in acutely relapsed patients, aripiprazole is efficacious in the treatment of global psychopathology, in improving the likelihood of clinical response (eg, ≥20% improvement on rating scales of global psychopathology), and in improving the positive symptoms of schizophrenia (955). The evidence that negative symptoms improve with aripiprazole treatment is less clear, as significant improvement with aripiprazole, compared with placebo, is less consistently found across doses of drug and studies (955) | + |
| Singh J, Kour K, Jayaram MB. Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database Syst Rev 2012;1:CD007967. | ACE inhibitors | The results seem to favour the use of acetylcholinesterase inhibitors in combination with antipsychotics on a few domains of mental state and cognition, but because of the various limitations in the studies as mentioned in the main text, the evidence is weak | As such, there is currently insufficient evidence to support the usefulness of these agents in improving cognitive performance in schizophrenia | – |
| Dold M, Li C, Tardy M, et al. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev 2012;11:CD006391. | Benzodiazepines | There is currently no convincing evidence to confirm or refute the practice of administering benzodiazepines as monotherapy or in combination with antipsychotics for the pharmacological treatment of schizophrenia and schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines are effective for very short-term sedation and could be considered for calming acutely agitated people with schizophrenia | Wolkowitz and Pickar (224) reviewed double-blind studies of benzodiazepines as monotherapy and found that positive effects (reductions in anxiety, agitation, global impairment, or psychotic symptoms) were reported in nine of 14 studies. Double-blind studies evaluating benzodiazepines as adjuncts to antipsychotic medications were also reviewed by Wolkowitz and Pickar (224). Seven of 16 studies showed some positive effect on anxiety, agitation, psychosis or global impairment; 5 of 13 showed efficacy in treating psychotic symptoms specifically | 0 |
| Matar HE, Almerie MQ, Sampson S. Fluphenazine (oral) versus placebo for schizophrenia. Cochrane Database Syst Rev 2013;:CD006352. | Fluphenazine | Fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia | If a long-acting injectable medication is indicated, the oral form of the same medication (ie, fluphenazine, haloperidol and risperidone in the USA) is the logical choice for initial treatment during the acute phase | – |
| Donnelly L, Rathbone J, Adams CE. Haloperidol dose for the acute phase of schizophrenia. Cochrane Database Syst Rev 2013;:CD001951. | Haloperidol | No results were conclusive and all were based on small, short studies of limited quality. However, it would be understandable if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses | Table 2. 5–20 mg/day | 0 |
| Adams CE, Bergman H, Irving CB, et al. Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev 2013;:CD003082. | Haloperidol | Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should be less favoured as a control drug for randomised trials of new antipsychotics | High-potency first-generation antipsychotic medications, such as haloperidol and fluphenazine, are more commonly prescribed than low-potency compounds (803). Although these medications have a greater tendency to cause extrapyramidal side effects than the low-potency medications, such as chlorpromazine and thioridazine, their side effects are easier to manage than the sedation and orthostatic hypotension associated with low-potency agents | – |
| Asmal L, Flegar SJ, Wang J, et al. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2013;:CD006625. | Quetiapine | Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators). Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone | Table 4 shows a similar side effects profile as the cochrane study | + |
| Khanna P, Suo T, Komossa K, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2014;:CD006569. | Aripiprazole | Information on all comparisons is of limited quality, is incomplete and problematic to apply clinically. The quality of the evidence is all low or very low. Aripiprazole is an antipsychotic drug with an important adverse effect profile | Not specifically addressed. Only addresses studies comparing aripiprazole to placebo and first-generation antipsychotics | 0 |
| Adams CE, Awad GA, Rathbone J, et al. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev 2014;:CD000284. | Chlorpromazine | Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative and mood symptoms | 0 |
| Wang J, Sampson S. Sulpiride versus placebo for schizophrenia. Cochrane Database Syst Rev 2014 CD007811 | Sulpiride | Sulpiride may be an effective antipsychotic drug but evidence of its superiority over placebo from randomised trials is very limited | The only randomised, controlled trial used sulpiride, a dopamine receptor antagonist similar to first-generation antipsychotics that is available in Europe but not in North America. Shiloh et al (1131) added placebo or sulpiride, titrated up to a dose of 600 mg/day, to clozapine for 10 weeks in the treatment of 28 partially responsive patients who were taking stable doses of clozapine and who had BPRS scores >42. The sulpiride group had significantly greater decreases in BPRS (15%), Scale for the Assessment of Negative Symptoms (10%) and Scale for the Assessment of Positive Symptoms (12%) scores | 0 |
| Leucht S, Helfer B, Dold M, et al. Carbamazepine for schizophrenia. Cochrane Database Syst Rev 2014;:CD001258. | Carbamazepine | Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified—especially if focusing on people with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities | A number of studies of the efficacy of carbamazepine and valproate in schizophrenia have been done. Excluding findings suggesting their use in treating patients whose illness has strong affective components, the evidence is quite convincing that neither agent, used alone, is of significant value in the long-term treatment of schizophrenia | + |
| Tardy M, Dold M, Engel RR, et al. Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014 CD009396 | Trifluoperazine | The results did not show a difference in efficacy between trifluoperazine and low-potency antipsychotics. Trifluoperazine produced more movement disorders | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative and mood symptoms | + |
| Tardy M, Huhn M, Kissling W, et al. Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014.CD00926822 | Haloperidol | We found no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative and mood symptoms | + |
| Tardy M, Huhn M, Engel RR, et al. Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014 CD009230 | Fluphenazine | Fluphenazine was not significantly different from low-potency antipsychotic drugs in terms of response to treatment | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative and mood symptoms | + |
| Tardy M, Huhn M, Engel RR, et al. Perphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014 CD009369 | Perphenazine | The results do not show a superiority in efficacy of high-potency perphenazine compared with low-potency first-generation antipsychotics | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative and mood symptoms | + |
| Dold M, Samara MT, Li C, et al. Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database Syst Rev 2015 CD009831 | Haloperidol | In efficacy-related outcomes, there was no clear evidence of a difference between the prototypal drug haloperidol and other, mainly high-potency first-generation antipsychotics | With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative, and mood symptoms | + |
| Buckley LA, Maayan N, Soares-Weiser K, et al. Supportive therapy for schizophrenia. Cochrane Database Syst Rev 2015;:CD004716. | Supportive therapy | There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy, but these findings are based on a few small studies where we graded the evidence as very low quality | In a review of three studies, Rector and Beck (188) reported a large aggregated effect size favouring studies, Rector and Beck (188) reported a large aggregated effect size favouring cognitive-behavioural therapy over supportive therapy for reducing negative symptoms | 0 |
| Almerie MQ, Okba Al Marhi M, Jawoosh M, et al. Social skills programmes for schizophrenia. Cochrane Database Syst Rev 2015;:CD009006. | Social skills Programmes | Studies are still so limited that this package of care has to be thought of as experimental. There is no indication that these social skills programmes do harm and some that they do good | Social skills training has been found helpful in addressing functional impairments in social skills or activities of daily living. The key elements of this intervention include behaviourally based instruction, modelling, corrective feedback and contingent social reinforcement | 0 |
| Dougall N, Maayan N, Soares-Weiser K, et al. Transcranial magnetic stimulation (TMS) for schizophrenia. Cochrane Database Syst Rev 2015;:CD006081. | Transcranial magnetic stimulation | There is insufficient evidence to support or refute the use of TMS to treat symptoms of schizophrenia | Although these findings of potential benefits of rTMS in schizophrenia and other psychotic disorders are interesting and worthy of future research, rTMS has not been approved for use in patients with schizophrenia, and there is insufficient evidence to recommend its use in clinical practice | Yes |
| Shek E, Stein AT, Shansis FM, et al. Day hospital vs outpatient care for people with schizophrenia. Schizophr Bull 2009;35:1057–8. | Day hospital | Evidence is limited and dated. Day hospital care may help avoid inpatient care but data are lacking on missing on a raft of outcomes that are now considered important, such as quality of life, satisfaction, healthy days and cost | Controlled studies have shown that day hospitalisation is at least as effective as acute inpatient care, and in some studies more effective, in such measures as decreasing symptoms and the rehospitalisation rate and better preserving role functioning (562, 563, 573, 601–609) | 0 |
| Pharoah F, Mari J, Rathbone J, et al. Family intervention for schizophrenia. Cochrane Database Syst Rev 2010;:CD000088. | Family intervention | Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy-makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality | All evidence-based approaches emphasise the value of family participation in treatment and stress the importance of working together in a collaborative endeavour. The main goal of family interventions, referred to as ‘psychoeducation’, is to decrease the risk of the patient’s relapse | + |
| Xia J, Merinder LB. Psychoeducation for schizophrenia. Cochrane Database Syst Rev 2011.CD002831 | Psychoeducation | Psychoeducation does seem to reduce relapse, readmission and encourage medication compliance, as well as reduce the length of hospital stay in these hospital-based studies of limited quality. The true size of effect is likely to be less than demonstrated in this review—but, nevertheless, some sort of psychoeducation could be clinically effective and potentially cost beneficial | The main goal of family interventions, referred to as ‘psychoeducation’, is to decrease the risk of the patient’s relapse. More recent research has emphasised other goals, such as improving patient functioning, decreasing family burden and improving family functioning | + |
| Marshall M, Crowther R, Sledge WH, et al. Day hospital versus admission for acute psychiatric disorders. Cochrane Database Syst Rev 2011;:CD004026. | Day hospital | Caring for people in acute day hospitals is as effective as inpatient care in treating acutely ill psychiatric patients. However, further data are still needed on the cost-effectiveness of day hospitals | Controlled studies have shown that day hospitalisation is at least as effective as acute inpatient care, and in some studies more effective, in such measures as decreasing symptoms and the rehospitalisation rate and better preserving role functioning (562, 563, 573, 601–609) | + |
| Jones C, Hacker D, Cormac I, et al. Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia. Cochrane Database Syst Rev 2012;:CD008712. | Cognitive-behavioural therapy | Trial-based evidence suggests no clear and convincing advantage for cognitive-behavioural therapy over other—and sometime much less sophisticated—therapies for people with schizophrenia | Therefore, based on the available evidence, persons with schizophrenia who have residual psychotic symptoms while receiving adequate pharmacotherapy may benefit from cognitive behaviorally oriented psychotherapy | 0 |
(+) indicates congruence between the study and Cochrane database recommendations. (−) indicates no congruence among the study and Cochrane Database. (0) indicates unable to determine due to nature of the individual study analysed.