Bipolar disorder is characterized by a constitutional predisposition to mood instability, with alternating depressive and expansive phases. Mood fluctuations correspond to variable periods characterized by a tendency toward behavioral inhibition or excitement. The clinical expression of bipolar disorder is extremely variable and ranges from problematic temperament to acute and chronic psychotic conditions. The clinical picture varies according to the frequency, intensity, and duration of affective, cognitive, and behavioral manifestations.
In addition to classic Bipolar I Disorder, characterized by manic or mixed episodes with or without major depression, this spectrum includes psychotic forms, including schizoaffective variants, and Bipolar II Disorder, characterized by recurrent major depression associated with attenuated, hypomanic expansive phases. The latter represents the most common phenotype of bipolar disorder and is frequently underdiagnosed. Other variants within the Bipolar II spectrum include major depressive episodes overlapping with cyclothymic or hyperthymic temperamental characteristics. Furthermore, the literature is unanimous in maintaining that depressed patients who switch into hypomania following treatment with antidepressants also belong to the bipolar spectrum 6,10,12,15.
Residual Symptoms
The acute phases of bipolar disorder—depressive, manic, or mixed episodes—may be preceded by prodromal symptoms and may remain “open” after the gross remission of the acute symptomatology, with the persistence of residual symptoms. It is also possible that therapeutic intervention may fail to completely resolve certain symptomatic aspects of the illness, or that some psychosocial functioning problems may arise as a result of the disorder’s impact on environmental and interpersonal adaptation.
With regard to depressive features, the residual symptoms described include irritable mood, a low threshold for anxiety, social withdrawal and reduced affective resonance, decreased behavioral vitality, reduced baseline energy levels, unstable self-esteem, and fear of relapse. Depressive residual symptoms may occur in both unipolar and bipolar depression and are found in both Bipolar I and Bipolar II presentations. The number and duration of episodes, as well as the presence of prodromal symptoms, are predictive of post-episode residuality 2–7,13,15,16.
Following resolution of the manic phase, hyperactivity, impulsivity, irritability, and increased initiative may persist. These symptoms can produce friction and conflict with the surrounding environment in the absence of a facilitating context. In other cases, subtle depressive symptoms may remain after a severe expansive phase, such as feelings of guilt about past behavior, insecurity, apprehension or worry, difficulty establishing normal social relationships, and consequent alienation from everyday contexts 7.
Residual Syndromes
The concept of residual symptomatology following an acute phase does not correspond to the concept of syndromic residuality of a disorder. Residual syndromes of a disorder should not be understood primarily as the transient or persistent presence of features belonging to the active phases, albeit at reduced intensity. Rather, they consist of clusters of symptoms and signs that develop as a consequence of the disorder and the biological process underlying it, and that persist beyond the acute phases of the illness.
In bipolar disorder, these may include cognitive, affective, and behavioral changes produced by the pathological process underlying mood instability and excitability. These clinical features affect inter-episode adaptation and quality of life, even in the presence of stable clinical remission, and may sometimes indirectly influence the course of the illness, treatment adherence, and response to therapy.
From a psychopathological perspective, the conceptualization of residual syndromes differs from that used to describe residual symptoms of an acute phase. The latter can be described by referring to an objective and generally shared concept of “euthymia”, corresponding to normal functioning, social interaction, productivity, and autonomy, together with the absence of medically, socially, or legally risky behaviors.
Thus, a depressive residual state may be understood as an incomplete recovery relative to a normal level of functioning (Figure 1), whereas a manic residual state may be understood as a residual excess relative to the same reference level (Figure 2). Residual symptoms relate to their respective acute phases in the same way that the acute phases relate to euthymia, and therapeutic intervention often consists of optimizing the same treatments used during the acute phases of the disorder.
Residual syndromes, on the other hand, represent an autonomous and independent process that tends to become detached from the original mood episodes and requires specific intervention.
Figure 1 — Figure 2
Bipolar I Disorder: Psychosocial Deficit
As early as 1921, Kraepelin observed that: “when manic-depressive illness has persisted for some time and the attacks have recurred frequently, the psychological change becomes evident even during the intervals between episodes” 18.
This residual deficit syndrome of bipolar disorder has not been adequately described in recent literature. In some cases, deficit symptomatology becomes confused with the social and occupational consequences of particularly severe bipolar disorder.
Some severe bipolar forms, characterized by early-onset psychotic phases and a high frequency of episodes, initially present with classic expansive and depressive episodes, followed by residual features characterized by cognitive deficits, affective flattening, and reduced interests and initiative that closely resemble residual schizophrenic states. In particular, reduced volitional drive and impaired cognitive performance tend to become stable and acquire a course independent of the major episodes.
This type of residual state represents a genuine “scar” left by acute episodes and is more common when the episodes are psychotic, manic, or mixed in nature. In this regard, Angst reported a 15% incidence of organic mental syndromes among patients with manic-depressive illness. This incidence was reportedly even higher among older adults, reaching approximately 23% 11.
According to some authors, the pathogenesis of these deteriorative conditions may also be influenced by complications of the primary affective disorder, such as alcoholism, substance use, and behaviors carrying risks for vascular, metabolic, and other diseases.
Bipolar II Disorder: Hypophoric Syndrome
In Bipolar II Disorder, the process of affective activation is generally contained, often ego-syntonic, and may produce a further residual phenomenon that is qualitatively different from the deficit syndromes resulting from severe psychotic manic or mixed episodes.
At times, after the resolution of hypomanic excitement, when the person returns to an objective level of euthymia, subjective equilibrium is not restored, corresponding to a satisfactory level of gratification 1,2,13,16.
Frequently, pathological manic or hypomanic excitement is accompanied by a subjective state of heightened attunement, pleasure, and gratification and is therefore experienced as desirable. Moreover, the amplified gratification associated with affective elevation and the subjective experience of control over the environment leaves a strong mnemonic imprint even after the phase has ended (Figure 3).
The euphoric or excited experience therefore creates a different hedonic memory from that which existed previously. The reference level used to define subjective “well-being” is no longer equivalent to an objective state of equilibrium but instead corresponds to the excited state (Figure 4).
If this new “calibration” of the reward system persists, a person in remission from the euphoric phase will no longer find a euthymic state sufficiently satisfying and may seek, despite the associated risks and consequences, a hypomanic state of adaptation.
At a rational level, the individual is able to recognize the benefits resulting from stability and reduced reactivity, the reduction in the risk of relapse, and the consistency of social and productive gains achievable in a state of equilibrium. At the affective and behavioral levels, however, a tendency may develop to reproduce or facilitate excitement, effectively “rowing against” spontaneous or treatment-induced stabilization.
Figure 3 — Figure 4
Environmental resources available under conditions of equilibrium may appear uninteresting, or at least no longer sufficiently interesting. They may be objectively appreciated but fail to generate enthusiasm or motivate a sense of momentum. The feelings elicited by the environment, which often dominate the patient’s leisure time, include boredom, dissatisfaction, and lack of stimulation.
The person may remain normally responsive to ordinary contexts involving entertainment or pleasure, yet still tend not to seek them out or may initially reject them because they are not associated with intense anticipatory pleasure.
The subjective experience centers on the idea that the environment neglects the patient and fails to stimulate them with sufficient intensity and salience, thereby forcing them into a kind of hedonic lethargy. Feelings of hostility toward others may arise, with others being blamed for being uninteresting, unstimulating, or unengaging—or for no longer being so as they once were.
If the condition persists, retrospective recollection of the gratification experienced during the period of excitement, together with the loss of that gratification, may become the predominant idea and may be associated with fear or anguish about never being able to return to hyperphoria and being condemned to hypophoria—the “lost paradise” syndrome.
In order to achieve a subjectively acceptable level of hyperphoria, patients may turn to psychoactive substances, seek intense and unusual stimuli, or seek otherwise ordinary stimuli—such as a relationship—within a problematic and risky context that restores their salience, which would otherwise be insufficient.
This may include involvement in “conflictual,” “stormy,” or “secret” romantic and sexual relationships, accompanied by disinterest or indifference toward relationships or approaches that develop in a normal manner.
In practice, the hypophoric individual tends to adopt strategies aimed at enhancing familiar stimuli in order to reconstruct a sense of intensity or “edge” around them. In the absence of such opportunities, there may be an apparently closed attitude toward relationships, which the patient explains by claiming that there are no engaging people or approaches around them.
This aspect of bipolar chronicity may become so pervasive that it constitutes a pathology within the pathology itself, which can be described as a kind of “addiction to hyperphoria.”
From a nosographic perspective, the residual presentation of Bipolar II Disorder resembles two previously described conditions, both closely related to bipolar disorder itself.
The first is atypical depression, characterized by mood reactivity and interpersonal sensitivity, frequently accompanied by comorbidity with anxiety disorders, impulse-control disorders, personality disorders, bulimia, or alcohol and substance abuse 6,10,15.
There is also often a discrepancy between the patient’s drive and initiative, which are depressed, and their imaginative activity, which is normal or enhanced (daydreaming).
From a hedonic perspective, consummatory pleasure is generally sufficiently preserved, whereas anticipatory hedonic activation—the process that drives the individual toward contact with stimuli—is reduced in relation to ordinary stimuli but may show marked increases in response to particular forms of stimulation.
As a consequence of this symptomatic picture, the longitudinal course of patients with atypical depression is often consistent with Bipolar II Disorder, with depressive phases alternating with brief expansive hypomanic phases or occurring within a cyclothymic temperament, and is usually associated with a “stormy” life history.
The other condition comparable to the bipolar residual state is the “hypophoric syndrome” described by Martin in individuals in remission from chronic heroin dependence 9,17.
Although post-heroin hypophoria contains some features associated with chronic opioid intoxication, attributable to residual impairment of the opioid system, the central and most refractory element consists of reduced gratification and lack of interest in the environment. This often precedes relapse into opioid use or the use of other substances such as cocaine, benzodiazepines, or alcohol.
Relapse into substance use often occurs at the culmination of an apparently reconstructive process involving the individual’s social role, in which, however, there has been no corresponding restoration of the level of gratification.
The former drug-dependent individual therefore regains some of their functions from a rehabilitative perspective, but experiences boredom and dissatisfaction, accompanied, at times, by a paroxysmal return to the search for intense, albeit fleeting and dysfunctional, stimulation through substances.
Here too, in stark contrast with the objective disruption caused by drug dependence, the hedonic memory of the period of substance use becomes the reference point for subjectively defining well-being and supports drug-seeking behavior.
A similar syndrome is also common in substance-use disorders regardless of the substance involved and may constitute the true point of “no return” in disorders of gratification.
Even when effective, anti-bipolar treatments may fail, particularly in advanced stages, to resolve the discrepancy between hedonic memory and functional euthymia.
Furthermore, successfully treated patients may dislike or complain that stabilization corresponds to the abolition of affective reactivity, ease of becoming enthusiastic, and intensity of activation toward the environment that had been part of the pathological or premorbid state.
The chronicity of such an experience may motivate patients to discontinue treatment on their own, with a predictably negative effect on the course of the disorder.
Treatment
At present, there are no established data regarding the use of specific therapies aimed at correcting bipolar residuality.
With regard to residual depressive symptoms, there are substantial doubts about the use of antidepressant pharmacotherapy, since these compounds are often implicated in the development of rapid cycling, mixed states, and chronicity.
More interesting are dopaminergic agents, such as MAO inhibitors, bupropion, and dopamine agonists, given the relationship between the dopaminergic system and reward.
These compounds may be used successfully to treat residual depression or symptoms such as anhedonia, reduced initiative, and difficulties with socialization.
Unfortunately, these medications are also not free from the risk of inducing manic switches and rapid cycling, and they may additionally be associated with the progressive development of tolerance.
Transient responses are therefore often observed, followed, after a variable period ranging from several weeks to several months and sometimes years, by depressive relapses that are frequently treatment-resistant and have a chronic course 8,14.
With regard to residual manic symptoms, optimization of mood-stabilizing treatment may allow good control of the affective component and psychomotor agitation. More problematic is the control of impulsivity and risk-taking behaviors, as well as residual psychotic symptoms such as grandiose ideas, pathological lying, and related phenomena.
Here too, the use of antipsychotics may precipitate depressive phases and trigger iatrogenic chronicity through extrapyramidal symptoms, tardive dyskinesia, and supersensitivity psychosis.
Residual deficit-type syndromes probably require a combined pharmacological and psychosocial-rehabilitative intervention, although to date no specific therapeutic strategy has been adequately studied.
For residual hypophoric states, maintaining prolonged treatment under conditions of affective stability and normal environmental stimulation may, over time, improve the patient’s level of subjective satisfaction.
Likewise, unplanned and unusual environmental changes may resolve a hypophoric residual state that would otherwise tend to persist.
In any case, maintaining and optimizing effective anti-bipolar treatment is essential as a foundation for considering other forms of therapeutic improvement. Consequently, neither residual symptoms of acute phases nor the specific post-excitatory residual state associated with the disorder constitute valid reasons for discontinuing ongoing mood-stabilizing treatment.
Conclusions
Beyond the residual symptoms of expansive and depressive phases, which are more readily understood, there is a form of syndromic residuality in bipolar disorder that has been less extensively studied and for which specific therapeutic strategies have not yet been adequately explored.
The residual syndrome following severe psychotic expansive or mixed phases shares certain features with the schizophrenic residual state, including some clinical characteristics and aspects of the therapeutic approach.
Post-hypomanic hypophoria in Bipolar II patients, unlike residual depression, is not in itself a deficit relative to euthymic equilibrium. Rather, it represents a discrepancy between objective euthymia and subjective gratification that develops after the patient has experienced expansive phases.
In this case, we are dealing with a post-excitatory syndrome that persists under conditions of affective equilibrium.
Its clinical expression shares certain features with bipolar depression and shares the core disturbance of gratification with the residual states associated with substance-use disorders (hypophoria).
The impact of this induced syndromic condition forms part of the course of the illness itself. It influences outcomes in terms of quality of life and, at times, treatment adherence and the relationship with substance abuse.
There are no specific therapeutic interventions for this condition, with the possible exception of the passage of time during effective treatment, which often allows long-term benefits to emerge without the need for additional therapeutic tools.