Background: There has been an appreciable increase in the prescribing efficiency of proton pump inhibitors, statins, and renin-angiotensin inhibitor drugs in Sweden in recent years. This has been achieved through multiple reforms encouraging the prescription of generics at low prices versus patented drugs in the same class. Generic venlafaxine also presents an opportunity to save costs given the prevalence of depression. However, depression is more complex to treat, with physicians reluctant to change prescriptions if patients are responding to a particular antidepressant. Objectives: We assessed (a) changes in the utilization pattern of venlafaxine versus other newer antidepressants before and after the availability of generic venlafaxine and before and after the initiation of prescription restrictions for duloxetine limiting its prescription to refractory patients, (b) utilization of generic versus original venlafaxine after its availability, and (c) price reductions for generic venlafaxine and the subsequent influence on total expenditure on newer antidepressants over time. Methodology: We performed interrupted time series analysis of changes in monthly reimbursed prescriptions using defined daily doses (DDDs) of patients dispensed at least one newer antidepressant from January 2007 to August 2011. DDDs was defined as the average maintenance dose of a drug when used in its major indication in adults. This included 19 months after the availability of generic venlafaxine and before initiation of prescription restrictions for duloxetine to 13 months after prescription restrictions. Total expenditure and expenditure/DDD for venlafaxine were measured over time. Results: No appreciable change in the utilization pattern for venlafaxine was observed after generic availability when no appreciable demand-side activities by the regions (counties) were implemented to encourage its use. The utilization of venlafaxine significantly increased after prescription restrictions for duloxetine. Generic venlafaxine was dispensed once available, reaching 99.6 % of total venlafaxine (DDD basis) by August 2011. There was an appreciable fall in expenditure for newer antidepressants in Sweden after generic venlafaxine despite increased utilization, helped by a 90 % reduction in expenditure/DDD for venlafaxine by the end of the study versus prepatent loss prices. Conclusion: Multiple demand-side measures are needed to change physician prescribing habits. Authorities should not rely on a spillover effect between drug classes to effect change. Limited influence of prescription restrictions on the subsequent utilization of duloxetine reflects the complexity of this disease area. This is exacerbated by heterogeneous indications for duloxetine.