Can prednisone cause feeling unwell or 'feeling like shit' as a side effect?

Yes, prednisone commonly causes multiple symptoms that make people "feel like shit"

Prednisone causes a wide range of adverse effects that significantly impact how patients feel, including psychiatric symptoms (mood swings, insomnia, irritability, depression), physical symptoms (weight gain, increased appetite, fatigue, weakness), and metabolic disturbances—all of which contribute to an overall sense of feeling unwell 1.

Psychiatric and Neurological Effects

The FDA label explicitly lists extensive neuropsychiatric adverse reactions that directly explain why patients feel terrible 1:

• Mood disturbances: Depression, emotional instability, irritability, mood swings, euphoria (paradoxically), mania
• Cognitive impairment: Impaired cognition, memory deficits, decreased concentration, mental confusion, delirium, dementia-like symptoms
• Sleep disruption: Insomnia (one of the most commonly reported side effects on social media) 2
• Psychological symptoms: Anxiety, restlessness, personality changes, withdrawn behavior
• Severe reactions: Psychosis, hallucinations, schizophrenia, severe depression

Research confirms these effects are dose-dependent and typically emerge within the first few weeks of therapy 3, 4. Short-term therapy (like prednisone bursts) more commonly causes hypomania and euphoria, while long-term therapy tends to induce depressive symptoms 3, 4. Even brief courses at modest dosages cause statistically significant mood changes, primarily manic symptoms rather than depressive ones 5.

Physical Symptoms Contributing to Feeling Unwell

The FDA label documents numerous physical adverse effects 1:

• Weight gain and appetite changes: Increased appetite, weight gain, moon face, buffalo hump, cushingoid appearance
• Gastrointestinal: Nausea, abdominal pain, gastric irritation, diarrhea or constipation
• Musculoskeletal: Muscle weakness, myalgias, arthralgias, fatigue, steroid myopathy
• Metabolic: Hyperglycemia, fluid retention, electrolyte imbalances
• General malaise: Fatigue, pyrexia, general sense of unwellness

Weight gain is particularly distressing to patients—it ranks as the #1 concern for patients (4th for clinicians) and is the most commonly reported side effect on patient forums like PatientsLikeMe and Twitter 2. Among 4,950 prednisone users on PatientsLikeMe, weight gain (n=435) and increased appetite (n=108) were the most frequently reported adverse effects 2.

Important Clinical Considerations

Dosage matters: The incidence of adverse effects is directly related to dose, though not to timing, severity, or duration of symptoms 4. Higher doses increase the risk of feeling worse.

Timing: Symptoms frequently present early in treatment (first few weeks) and typically resolve with dose reduction or discontinuation 3, 4.

Individual variation: Females and those with prior corticosteroid-induced psychiatric side effects are at higher risk 6. However, the elderly and those with previous psychiatric diagnoses are NOT at increased risk for psychiatric side effects 6.

Paradoxical effects: Some patients with depression may actually experience improvement in depressive symptoms during prednisone therapy rather than worsening 5. However, patients with PTSD may experience increases in depression and traumatic memories 5.

Management Approach

When patients report feeling terrible on prednisone:

1. Validate their experience—these are well-documented, common adverse effects
2. Assess specific symptoms: Distinguish between psychiatric (mood, sleep, cognition), physical (weight, weakness, GI), and metabolic effects
3. Consider dose reduction if clinically feasible—symptoms are dose-dependent and often improve with lower doses 1, 3
4. For severe psychiatric symptoms: Antipsychotics, mood stabilizers (lithium, lamotrigine), or anti-seizure medications may be needed 3
5. Do not abruptly discontinue—taper gradually to avoid adrenal insufficiency 1

The bottom line: Feeling like shit on prednisone is an expected, well-documented phenomenon affecting multiple body systems simultaneously, not a sign of weakness or unusual sensitivity.