Natural Medicines for Psychotic Disorders
In 110 randomized controlled trials, evidence was found for glycine, sarcosine, N-acetylcysteine, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol, and vitamin B6 to improve psychotic symptoms when added to antipsychotics. Ginkgo biloba and vitamin B6 seemed to reduce tardive dyskinesia and akathisia.
We found inconclusive or no evidence for omega-3 fatty acids, D-serine, D-alanine, D-cycloserine, other B vitamins, vitamin C, DHEA, PREG, inositol, GHB, and des- tyr-gamma-endorphin when added to antipsychotics. Reserpine with- out antipsychotics seemed effective in one old study but was poorly tolerated.
Glycine and sarcosine combined with antipsychotics may reduce negative symptoms, but not when combined with clozapine and neither as monotherapy. Inconclusive evidence was found for D-cycloserine and D-serine on clinical improvement. Our results concur with two reviews (Singh and Singh, 2011; Tsai and Lin, 2010) and are in line with a Cochrane review (Tiihonen and Wahlbeck, 2006). Conflicting results from studies on drugs targeting the glutamate/NMDA system may be explained by complicated dose-effect relationships, as recently found in studies with the GlyT-1 transporter antagonist bitopertin (Umbricht et al., 2013).
All three studies combining sarcosine with antipsychotics (not clozapine) found positive effects in almost all symptom domains (Lane et al., 2005, 2010; Tsai et al., 2004). When combined with cloza- pine (one study), no treatment effects were found (Lane et al., 2006). In addition, when given without antipsychotics (one study), sarcosine did not improve symptoms (Lane et al., 2008). Sarcosine did not improve adverse effects of antipsychotics in four (from four) studies (Lane et al., 2005, 2006, 2010; Tsai et al., 2004). Adverse effects of sarcosine included weight gain, insomnia, palpitations, dizziness, and sedation.
One large study on NAC added to antipsychotics reported im- proved positive symptoms but no improvement of negative, cognitive, or general symptoms and no improvement of adverse effects of antipsy- chotics (Berk et al., 2008), whereas one small study found some improvement of cognitive symptoms (Lavoie et al., 2008). The large study (Berk et al., 2008) reported that there were no adverse effects, and in the small study (Lavoie et al., 2008), occurrence of any adverse effect was not mentioned.
Ginkgo biloba seems to benefit patients with schizophrenia in several ways when added to antipsychotics. Several studies sug- gested evidence for improving symptoms in various domains, espe- cially an effect on positive symptoms and the reduction of adverse effects of antipsychotics.
Inconsistent beneficial outcomes of studies on B vitamins were identified, especially when given as a combination of B1, B3, B6, B9, and/or B12 with antipsychotics. One review concluded that no adequate support for the efficacy of B vitamins in schizophrenia can be identified (Kleijnen and Knipschild, 1991). Most studies with positive effects in our review, however, were published after the aforementioned review was published. Most convincing evidence was found for vitamin B6 added to antipsychotics, shown to be effective in diminishing general psychopathology and TD.
By adding Chinese or ayurvedic herbs to antipsychotics, general psychopathology may improve. One study (of two) on artemisinin (a natural medicine against malaria) found a signifi- cant effect on negative symptoms and clinical global impression, but no effect on positive or cognitive symptoms or on general psy- chopathology in first-episode treatment-naive patients who were treated with risperidone (Wang et al., 2014; Dickerson et al., 2011). The study of Dickerson et al. (2011) did not demonstrate clinical benefit of adjunctive artemisinin for schizophrenia symp- toms. Rathbone et al. (2007) state that “the results suggest that combining Chinese herbal medicine with antipsychotics is benefi- cial.” Another Cochrane review (Agarwal et al., 2007) concludes that “ayurvedic medication may have some effects for treatment of schizophrenia, but has been evaluated only in a few small pio- neering trials.” These results need further exploration and pharma- cological differentation, as Chinese and ayurvedic herbs include hundreds of species combined in thousands of different combina- tions and are prescribed in a fundamentally different way than Western medicines (Clifford, 1994; Kaptchuck, 2000). The com- bined approach using knowledge from both conventional and Chinese medicine seems promising, as it may lead to innovation (Van der Greef, 2011) and possibly to improved outcomes (Zhang et al., 2011b).
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