Doxycycline may also be used as adjunctive therapy for severe acne. In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder. Can also be used in adjunctive therapy with pilocarpine or carbonic anhydrase inhibitors. Several studies have shown atypical antipsychotics to be effective both as single-agent and adjunctive treatments. Sucralfate is often used as an adjunctive therapy. AAS are without value as primary therapy but may be of value as adjunctive therapy. Phenytoin was to be used as adjunctive therapy only. Instead, chlorhexidine is more effective used as an adjunctive treatment with tooth brushing and flossing. Doses for this kind of adjunctive goal can be kept low, resulting in better tolerability. One of the most used drug in adjunctive therapy is dorzolamide. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Estradiol has been found to be effective in the adjunctive treatment of schizophrenia in women. More recently, it is under investigation as an adjunctive treatment in schizophrenia. However, a more recent trial found no benefit from adjunctive rifampicin. Medications to aid CBT have not been as encouraging with the exception of adjunctive D-clycoserine.