Computerized methods for drug-related side effect identification can help reduce costs and speed up drug development. Multisource data about drug and side effects are widely used to predict potential drug-related side effects. Heterogeneous graphs are commonly used to associate multisourced data of drugs and side effects which can reflect similarities of the drugs from different perspectives. Effective integration and formulation of diverse similarities, however, are challenging. In addition, the specific topology of each heterogeneous graph and the common topology of multiple graphs are neglected.We propose a drug-side effect association prediction model, GCRS, to encode and integrate specific topologies, common topologies and pairwise attributes of drugs and side effects. First, multiple drug-side effect heterogeneous graphs are constructed using various kinds of similarities and associations related to drugs and side effects. As each heterogeneous graph has its specific topology, we establish separate module based on graph convolutional autoencoder (GCA) to learn the particular topology representation of each drug node and each side effect node, respectively. Since multiple graphs reflect the complex relationships among the drug and side effect nodes and contain common topologies, we construct a module based on GCA with sharing parameters to learn the common topology representations of each node. Afterwards, we design an attention mechanism to obtain more informative topology representations at the representation level. Finally, multi-layer convolutional neural networks with attribute-level attention are constructed to deeply integrate the similarity and association attributes of a pair of drug-side effect nodes. Comprehensive experiments show that GCRS's prediction performance is superior to other comparing state-of-the-art methods for predicting drug-side effect associations. The recall rates in top-ranked candidates and case studies on five drugs further demonstrate GCRS's ability in discovering potential drug-related side effects.zhang@hlju.edu.cn. 

https://pure.rug.nl/ws/files/219408694/sbac037.pdf

OUP accepted manuscript

This review of commonly prescribed psychotropic drugs aims to update the clinician on possible ophthalmic side effects that may include dry eye, diplopia, mydriasis, and cataracts. This review summarizes our current knowledge of known ocular side effects of psychotropic drugs based on reviews, case reports, case-control studies, a case series, and cross-sectional observational studies reported in the recent literature. The review covers disorders related to depression, anxiety, and stress which are commonly encountered within society and can have debilitating impacts on an individual's quality of life that may require chronic therapeutic management. The main medications used in the treatment and management of these conditions typically target receptors, metabolic enzymes, or transport pumps that alter the pre- and/or post-synaptic levels of neurotransmitters such as serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, and opioids to improve mood and/or relieve pain and anxiety. Novel non-therapeutic options are undergoing clinical trials, and some patients may seek alternative therapies or have associated substance abuse issues to alleviate their symptoms. This review summarizes some of the clinical signs of depression and the main therapeutic options and their reported ocular side effects which may be pertinent today given the rise in use of psychotropic medications used to manage depression, anxiety, and stress. 

https://www.dovepress.com/getfile.php?fileID=78568

A Review of Ocular Complications Associated with Medications Used for Anxiety, Depression, and Stress

Schizophrenia is a complex and incompletely elucidated pathology that affects sensorimotor function and also produces numerous therapeutic challenges. The aims of this cross-sectional study were to identify the profile of neurological soft signs (NSS) in patients with predominantly negative symptoms of schizophrenia (PNS) compared with patients with schizophrenia who do not present a predominance of negative symptoms (NPNS) and also to objectify the impact of treatment on the neurological function of these patients. Ninety-nine (n = 99; 56 females and 43 males) patients diagnosed with schizophrenia according to DSM-V were included; these patients were undergoing antipsychotic (4 typical antipsychotics, 86 atypical antipsychotics, and 9 combinations of two atypical antipsychotics) or anticholinergic treatment (24 out of 99) at the time of evaluation, and the PANSS was used to identify the patients with predominantly negative symptoms (n = 39), the Neurological Evaluation Scale (NES) was used for the evaluation of neurological soft signs (NSS), and the SAS was used for the objectification of the extrapyramidal side effects induced by the neuroleptic treatment, which was converted to chlorpromazine equivalents (CPZE). The study’s main finding was that, although the daily dose of CPZE did not represent a statistically significant variable, in terms of neurological soft signs, patients with PNS had higher rates of NSS.

/pdf/the-impact-of-antipsychotic-treatment-on-neurological-soft-v4des0kz.pdf

The Impact of Antipsychotic Treatment on Neurological Soft Signs in Patients with Predominantly Negative Symptoms of Schizophrenia

http://www.aaojournal.org/article/S0161642023003068/pdf

Association of systemic medication use with glaucoma and intraocular pressure: the E3 Consortium.

Ocular side effects of antipsychotics receive little attention, and ophthalmological evaluation is routinely not recommended either before starting or during ongoing treatment with most psychotropics. Available literature suggests that the use of psychotropics is associated with the development of ophthalmological side effects that can be categorized into problems related to eyelid, cornea and conjunctiva, disorders of the uveal tract, accommodation problems, angle-closure glaucoma, cataract/pigmentary deposits in the lens and cornea, retinopathy, and other disorders.[1] Among all these adverse effects, angle-closure glaucoma can be very distressing and a medical-surgical emergency, especially while using medications with high anticholinergic properties. In this report, we discuss a patient who presented with psychotic symptoms, with a history of unilateral vision loss, who also had angle-closure glaucoma in the functional eye that got destabilized with the use of quetiapine. A 31-year male, 12th pass, single, working as a shopkeeper, who had a history of congenital hydrocephalus (that was surgically corrected with ventriculoperitoneal shunt placement), coarctation of the aorta, congenital glaucoma in both the eyes, developmental delay in the gross motor domain, slow to warm up temperament, bronchial asthma (diagnosed at the age of 2 years), and hypertension (diagnosed at the age of 10 years) presented with psychotic symptoms. His childhood history revealed that he had deficits in intellectual and adaptive functioning since early childhood but maintained well without much difficulty till 14 years. He was on regular treatment for glaucoma but unfortunately lost vision in his right eye at the age of 12, before starting any antipsychotics. Around the age of 15, he developed delusions of reference and persecution, auditory hallucinations, agitation, poor self-care, and negative symptoms, leading to significant psychosocial dysfunction. Over the years, he was treated with multiple psychotropics, including aripiprazole (up to 22.5 mg/day), olanzapine (5 mg/day, developed obsessive-compulsive symptoms), and quetiapine (350 mg/day) sequentially without much improvement. These medications often also led to an increase in intra-ocular pressure (IOP), leading to frequent changes in the medicines to manage the IOP and reduction in the doses of psychotropics by the family members. This time he presented with a relapse with similar psychotic symptoms. He was being treated with antihypertensives (telmisartan, metoprolol), antiglaucoma agents (dorzolamide, travoprost, netarsudil), salmeterol inhaler (for asthma), and quetiapine (350 mg/day) at the time of presentation to the inpatient unit. On physical examination, he was found to have a low hairline, wide-spaced canthi, flat nose, short neck, crooked irregular teeth, single palmar crease, sandal gap in feet, and hypospadias. Based on the history, differential diagnoses of other mental disorders due to brain damage and dysfunction versus schizophrenia, along with mild intellectual disability, were considered. The brain magnetic resonance imaging was suggestive of the Dandy walker variant (Blake’s pouch cyst) with corpus callosal and cerebral white matter thinning. His electroencephalogram did not reveal any abnormality. On psychometric assessment, his intelligence quotient was estimated to be 61. His IOP in the right eye (RE) was 28 mmHg, and his left eye (LE) was 20 mmHg after three days of admission. Initially, the dose of Tab Quetiapine was increased to 500 mg/day, with which his IOP in the left eye increased to 28 mm Hg and in the right eye to 32 mm Hg that was evaluated after 3 days of increasing the dose to 500 mg/day. No other medications (other than those mentioned before) with potential anticholinergic properties were given during this time. As a result, the dose of quetiapine was reduced to 250 mg/day, but his IOP in the left eye did not come down below 24 mm of Hg and in the right eye came down to 26 mm of Hg. He required rescue medications in the form of lorazepam during this period. Because of this, quetiapine was further tapered to 100 mg/day, and Tab Blonanserin 2 mg/day was initiated, with which IOP decreased to 20 mmHg. Later, Tab Quetiapine was stopped completely, and Tab Blonanserin was gradually increased to 10 mg/day over the next three weeks, with repeated monitoring of IOP, which ranged from 15 to 20 mmHg. Non-pharmacological measures in the form of psychoeducation, activity scheduling, and dietary modifications were initiated. With the change in antipsychotics and other actions, his positive and negative syndrome scale scores improved from (positive subscale-23; negative subscale score-25; general psychopathology-33 to positive subscale-15; negative subscale score-19, and general psychopathology-20) over four weeks. He was discharged after four weeks in an improved state. The average IOP ranges from 9 to 21 mm of Hg. Drugs with high anticholinergic properties are most commonly implicated in the development of angle closure or worsening of chronic angle-closure glaucoma. Regardless of the mechanism, this condition becomes an ophthalmological emergency to be promptly identified and managed.[1] Among various psychotropics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and typical antipsychotics like phenothiazines and diazepam are commonly known to precipitate angle-closure glaucoma.[1] A higher dose of antipsychotics with a high level of anticholinergic and antiadrenergic properties are risk factors for glaucoma. However, the exact effect of atypical antipsychotics on IOP is unclear, with some known to increase and some to decrease the IOP.[2] Clozapine, quetiapine, and olanzapine have been shown to have a protective effect in glaucoma via neurogenesis through stimulation of PI3K/Akt pathway and ERK phosphorylation.[3] However, clozapine and olanzapine show a high affinity for muscarinic receptors, which may exacerbate glaucoma.[3] Ziprasidone has been reported to increase IOP.[4] Quetiapine acts on various receptors including serotonin (5-HT1A, 2A, 2C), dopamine (D1-D5), histamine (H1), and adrenergic (a1, a2) receptors. Although rare, cases of cataract,[5] branch retinal vein occlusion,[6] and central serous chorioretinopathy[7] have been reported among patients receiving quetiapine. To our knowledge, there are no reports of raised IOP associated with quetiapine. In the present case, no other medications were changed when the dose of quetiapine was increased from 350 mg/day to 500 mg/day. Hence, the increase in IOP was attributed to the same. Further, the IOP came down when quetiapine was discontinued. Naranjo’s score[8] for the association was 7, indicating a possible association. However, the underlying Dandy Walker variant (Blake’s pouch cyst) and intellectual disability could have made our patient vulnerable to rise in IOP. Considering the fact that quetiapine is often used in elderly patients who also have glaucoma, the present association suggests that there is a need to monitor the IOP in patients receiving high doses of quetiapine. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. 

Quetiapine-induced raised intra-ocular pressure: An unusual entity

Through the years, the available psychopharmacological treatments have expanded with numerous new drugs. Besides weight gain, gastro-intestinal problems or Parkinson-like symptoms, ocular adverse effects of psychiatric drugs have been reported. These adverse effects are not common, but can be dangerous for the patient. This review summarises the current knowledge on the risk of raised intraocular pressure and glaucoma entailed by psychopharmacological treatment. Also, it provides updated data for clinicians involved in the treatment of patients with glaucoma or glaucoma risk factors. For this purpose, we performed an extensive literature search in the PubMed database using specific terms. Selective serotonin and noradrenaline reuptake inhibitors are the best evidenced as having no association with glaucoma. Antipsychotics, and especially first generation, seem to have no correlation with an increased intraocular pressure and therefore possibly with a risk of glaucoma, although a special attention should be paid when using ziprasidone. Tricyclic antidepressants, benzodiazepines and topiramate should be avoided in patients diagnosed with glaucoma or at risk. Clinicians should be aware of the possible psychotropic drug induced glaucoma and monitor at risk patients closely in order to prevent this condition. Irrespective of the psychopharmacological regimen taken into consideration, the glaucoma patient should be under the strict supervision of the ophthalmologist.

Otilia Maria Bolog

Papers

Psychopharmacological Treatment, Intraocular Pressure and the Risk of Glaucoma: A Review of Literature.