Background The practice patterns of psychiatrists have changed over the last two decades. Objectives This study describes the pattern of prescribing psychotropic drugs in treating common psychiatric disorders, and investigates the rate of polypharmacy and potential drug-drug interactions. Setting Psychiatry governmental outpatient clinic in the north of West Bank, Palestine. Methods Cross-sectional study that included all prescriptions which were issued over the period October 2018 to January 2019, for patients diagnosed with schizophrenia, depression, anxiety, bipolar disorder and schizoaffective disorders, and checked for the presence and the grade of potential drug-drug interactions using “Medscape drug interactions checker". Main outcome measure Prescribing patterns of psychotropic drugs. Results A total of 1045 prescriptions were examined. The mean age of the patients was 47.3 years (SD = 13.6), two-thirds of the patients (64.5%) were males. Fifty-two percent of the patients were diagnosed with schizophrenia while 15.2% were diagnosed with depression. The later third was diagnosed with bipolar disorder, schizoaffective and anxiety disorders (15.8%, 11.1% and 5.1% respectively). The most commonly prescribed drugs were typical antipsychotics for schizophrenia, bipolar and schizoaffective disorders, selective serotonin reuptake inhibitors for depression and tricyclic anti-depressants for anxiety. Polypharmacy was found in 877 prescriptions (84%), and drug-drug interactions (DDIs) were identified in 823 (94%) prescriptions. The DDIs were classified as minor (4, 0.5%), significant (418, 50.8%) and serious (401, 48.7%). Conclusions Our results suggest that the pharmacotherapy of psychiatric disorders in Palestine may not be in accordance to international guidelines and the incidence of polypharmacy and DDIs is high.