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6 - 12 Hours After Last Dose: Withdrawal Begins Onset of initial symptoms can include: Anxiety Muscle aches Increased tearing Insomnia Runny nose Excessive sweating Frequent yawning 24 - 48 Hours After Last Dose: Peak of Early Withdrawal Intensification of early symptoms and possible appearance of additional symptoms, such as: Agitation Diarrhea Heart palpitations High blood pressure Fever 72 Hours After Last Dose: Peak of Acute Withdrawal Typically, symptoms reach their peak in intensity and discomfort and can include: Nausea and vomiting Abdominal cramping Dilated pupils Goosebumps Blurred vision Rapid heartbeat 1 Week After Last Dose: Symptoms Begin to Subside At this time there is typically a gradual reduction in the intensity of physical symptoms, while psychological symptoms may persist or become more pronounced, including: Anxiety Depression Irritability Cravings for opioids 1 - 2 Weeks After Last Dose: Decrease in Physical Symptoms Most physical symptoms significantly diminish, while ongoing psychological and emotional challenges and the potential for continued cravings remain

These reductions represented estimated treatment differences ranging from 3.0% to 7.8% weight loss versus placebo, all of which were statistically significant

The HAMD score, for example, was 4.9 points higher in this endophenotype class as compared with the other patient group

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