European Journal of Cardiovascular Medicine

Generalized Anxiety Disorder (GAD) is a chronic psychiatric condition characterized by excessive and persistent worry, often accompanied by symptoms such as restlessness, fatigue, irritability, muscle tension, and sleep disturbances. It affects approximately 3–6% of the general population and is associated with substantial personal distress, functional impairment, and reduced quality of life. Despite its prevalence and clinical impact, GAD is often underdiagnosed and undertreated, particularly in primary care settings.

Pharmacological treatment is a mainstay of GAD management, especially for individuals with moderate to severe symptoms. Among the available options, Selective Serotonin Reuptake Inhibitors (SSRIs) are recommended as first-line pharmacotherapy due to their favorable balance of efficacy, tolerability, and safety. SSRIs function by increasing serotonergic neurotransmission, which is implicated in the pathophysiology of anxiety disorders. Agents such as escitalopram, sertraline, paroxetine, and fluoxetine are commonly prescribed and have been supported by numerous randomized controlled trials.

However, real-world data on the comparative effectiveness and tolerability of SSRIs in routine clinical practice remain limited. Understanding how patients respond to these agents outside of controlled research settings is crucial for optimizing treatment decisions and improving long-term outcomes.

This study aims to retrospectively evaluate the efficacy and tolerability of SSRIs in the management of GAD in a naturalistic clinical setting. By analyzing changes in anxiety symptoms over a 12-week treatment period and documenting adverse events, this study provides practical insights into the performance of SSRIs in everyday medical practice.

Study Design and Setting

This study employed a retrospective observational design and was conducted at the RVM Institute of Medical Sciences, located in Laxmakkapalli, Telangana, India. The data collection period spanned from January 2020 to December 2020. The study was approved by the Institutional Ethics Committee, and confidentiality of patient data was maintained throughout the process.

Study Population

A total of 100 adult patients diagnosed with Generalized Anxiety Disorder (GAD) and prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) were included in the study. Patient records were reviewed from the psychiatry outpatient department database. Inclusion and exclusion criteria were applied to ensure the relevance and reliability of the data.

Inclusion Criteria

Patients aged between 18 and 65 years.

Diagnosis of Generalized Anxiety Disorder (as per ICD-10/DSM-5 criteria).

Prescribed SSRIs as monotherapy.

Minimum follow-up period of 12 weeks with complete clinical documentation.

Exclusion Criteria

Patients with co-morbid psychiatric disorders (e.g., major depressive disorder, bipolar disorder, schizophrenia).

History of substance abuse or dependence.

Patients receiving concurrent psychotropic medications other than SSRIs.

Incomplete medical records or loss to follow-up before 12 weeks.

Data Collection and Variables

Data were extracted from patient case records, including:

Demographic details (age, gender).

Clinical history (duration of GAD, type of SSRI prescribed).

Efficacy outcomes assessed using the Hamilton Anxiety Rating Scale (HAM-A) at three time points: baseline, week 6, and week 12.

Adverse events and treatment discontinuation reasons as documented during follow-up visits.

Outcome Measures

The primary outcome was the change in HAM-A scores from baseline to week 12.
The secondary outcomes included the clinical response rate (≥50% reduction in HAM-A score), remission rate (HAM-A score ≤7), and tolerability profile based on reported adverse effects and discontinuation rates.

Statistical Analysis

Descriptive statistics were used to summarize demographic and clinical characteristics. Continuous variables (e.g., HAM-A scores) were expressed as mean ± standard deviation, while categorical variables (e.g., adverse events) were presented as frequencies and percentages.

The paired t-test was applied to evaluate changes in HAM-A scores over time. A p-value of <0.05 was considered statistically significant. Data analysis was performed using SPSS version 26.0.

A total of 100 patients diagnosed with Generalized Anxiety Disorder (GAD) who were prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) were included in this retrospective analysis. Data were extracted from electronic medical records over a 12-month period.

Demographic and Clinical Characteristics

The mean age of the participants was 35.6 ± 11.2 years, with an age range of 18 to 65 years. The sample consisted of 62% females and 38% males. The duration of GAD before the initiation of SSRI treatment ranged from 6 months to 5 years, with a mean duration of 2.3 ± 1.1 years. The most commonly prescribed SSRIs were escitalopram (38%), sertraline (32%), paroxetine (18%), and fluoxetine (12%) (Table 1).

Table 1: Demographic and Clinical Characteristics

Efficacy Outcomes

Treatment efficacy was evaluated using changes in Hamilton Anxiety Rating Scale (HAM-A) scores at baseline, week 6, and week 12. A progressive and significant reduction in HAM-A scores was observed over time, with mean scores decreasing from 25.4 ± 4.2 at baseline to 16.2 ± 3.9 at week 6 and 11.8 ± 3.5 at week 12 (Table 2).

Table 2: HAM-A Scores Over Time

The overall mean reduction in HAM-A score at 12 weeks was 13.6 points, representing a 53.5% decrease from baseline (p < 0.001). A clinical response (defined as a ≥50% reduction in HAM-A score) was observed in 68% of patients, while 34% achieved remission (HAM-A score ≤7) by week 12 (Table 3).

Table 3: Efficacy Outcomes

Tolerability and Adverse Events

SSRIs were generally well tolerated. The most frequently reported adverse events were nausea (20%), insomnia (14%), sexual dysfunction (12%), headache (10%), and fatigue (9%) (Table 4).

Table 4: Adverse Events

Treatment discontinuation due to adverse effects occurred in 7 patients (7%). Severe nausea accounted for 3 discontinuations, followed by intolerable insomnia (2 patients) and sexual side effects (2 patients) (Table 5). No serious adverse events or hospitalizations were reported during the study period.

Table 5: Discontinuation Details

Subgroup Analysis

In the gender-based analysis, female patients showed a slightly higher clinical response rate (71%) compared to males (63%), although this difference was not statistically significant (p = 0.18). Among the different SSRIs, escitalopram yielded the greatest mean reduction in HAM-A score (14.5 points), followed by sertraline (13.2 points), paroxetine (12.8 points), and fluoxetine (11.5 points) (Table 6).

Table 6: Subgroup Analysis

This retrospective study evaluated the real-world effectiveness and tolerability of Selective Serotonin Reuptake Inhibitors (SSRIs) in the treatment of Generalized Anxiety Disorder (GAD) over a 12-week period. A significant reduction in anxiety symptoms was observed, as reflected by the mean HAM-A score reduction of 13.6 points, representing a 53.5% decrease from baseline. These findings are consistent with previous controlled trials and meta-analyses that support the efficacy of SSRIs in anxiety management, including pediatric and adult populations [8, 13].

Among the SSRIs studied, escitalopram showed the greatest efficacy, followed by sertraline, paroxetine, and fluoxetine. This aligns with findings from Strawn et al. [8], who proposed pharmacogenetically guided escitalopram treatment for anxiety disorders, suggesting its high selectivity and favorable tolerability profile contribute to superior outcomes. Additionally, prior reviews have supported the broad efficacy and tolerability of escitalopram and other SSRIs across anxiety-related conditions [13].

In terms of tolerability, the adverse effects observed—such as nausea, insomnia, and sexual dysfunction—were consistent with those reported in earlier research [12]. The low discontinuation rate (7%) in this study also reflects the favorable side effect profile of SSRIs as documented in other reviews and retrospective analyses [9, 12]. Importantly, no serious adverse events or hospitalizations occurred during the treatment period.

Subgroup analysis revealed a slightly higher response rate among females compared to males, although the difference was not statistically significant. Previous studies have suggested that gender differences in pharmacokinetics and pharmacodynamics, as well as psychosocial variables, may influence treatment response [10], though larger studies are needed to confirm this trend.

A noteworthy observation from recent literature is that some patients with anxiety disorders remain untreated with SSRIs, despite clinical indications [11]. This highlights the importance of real-world studies like ours to bridge the gap between clinical guidelines and actual practice patterns.

The strengths of this study include its focus on naturalistic clinical outcomes and a clearly defined patient cohort. However, it is not without limitations. The retrospective design introduces potential bias related to missing or incomplete data, and the absence of a control group limits causal inferences. Additionally, long-term outcomes beyond the 12-week period were not assessed. Future prospective studies with randomized designs and extended follow-up are warranted to validate these findings and further refine SSRI treatment strategies for GAD.

Despite these limitations, our study contributes valuable insights into the routine use of SSRIs for GAD, particularly within an Indian clinical setting. Future prospective studies are needed to compare the long-term efficacy and safety of individual SSRIs and to identify patient-specific predictors of treatment response.

This retrospective study highlights the efficacy and tolerability of SSRIs in the management of Generalized Anxiety Disorder in a real-world clinical setting. A significant reduction in HAM-A scores was observed over 12 weeks, with a high response and remission rate, especially among patients treated with escitalopram. Adverse effects were generally mild and manageable, with a low discontinuation rate. These findings support the continued use of SSRIs as first-line pharmacological treatment for GAD. Despite limitations such as retrospective design and short follow-up, the results provide meaningful clinical insights. Future prospective and comparative studies are warranted to further optimize individualized treatment strategies for GAD.

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